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  • tropical
    replied
    Re: Swine flu vaccines, adjuvants, equity, safety

    #17:
    * "3. The adjuvant question. Two weighty objections to our advocacy of adjuvants have been advanced, one at FluTrackers and one by Jody Lanard here. They are slightly different but we will take them together. Vibrant62 at FluTrackers observes that the safety of adjuvants has been tested more often in the older age groups (where the immune response is more sluggish and adjuvants are more needed), not well tested in the young age groups. Vibrant62 suggests the decision doesn't have to be "all or nothing" but we could use unadjuvanted vaccine for some age groups (or pregnant women) and adjuvanted vaccine for others. Let's assume this is economically feasible (i.e., that two different vaccine could be made and distributed efficiently). If children and young adults really, on average, react quite differently to a particular adjuvant, then this will be seen in the safety and efficacy trials, unless it is rare, in which case we are in the same box we were earlier regarding trade-off with the benefit. There has been quite a lot of experience with adjuvants and influenza virus and also some with this particular virus. I will refer you to the excellent post by Vincent Racaniello at Virology Blog. Before giving my full answer to this, though, I want to address Jody Lanard's objections, since my answer is the same to both."
    ...
    ** "We may never know what the right thing to do was because we will be dealing with a counterfactual: what would the world have been like if we'd done X instead of Y?"
    **
    The WHO position is also to gather and find the most valuable and viable solution, based on the expertise of international scientific teams/professionals.

    So, the right thing to do, is to demand that the best option be vigorously suggested and sci. proved by the WHO, and than can be further implemented by the countries.


    *
    Is it the number of involved non-elderly people of various ages in the MF59 (EU aproved) adjuvant screening study enaugh balanced, that we can said at least that it is safe to use adjuvants at least in the age group 40-65, or not?

    Could we said that the ok registration of squalene/MF59 adjuvanted Fluad flu vacc., 2006. year, as already used seasonal flu vaccine in EU, is not due to less stringent safety laws than in US?

    Does the above already used adjuvanted vaccine, from the released scientific published trials, safe enaugh for the non-elderly age groups, at least for the senior adults from 30/40-65 years?



    _____________

    Probably, after there was other published results trials, but here we have an excerpt from an public doc about, here at FT, Vibrant62 given link of MF59 usage study, Fluad, pdf:
    http://www.flutrackers.com/forum/att...2&d=1251745072


    Sorry for the poor formated excerpted text:

    ____
    from one additional sticky link:

    http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_Discovery_PMC&li nkpos=1&log$=citedinpmcarticles&logdbfrom=pubmed

    1: Clin Vaccine Immunol. 2006 Sep;13(9):1010-3.

    Vaccines with the MF59 adjuvant do not stimulate antibody responses against squalene.


    <!--AuthorList-->Del Giudice G, Fragapane E, Bugarini R, Hora M, Henriksson T, Palla E, O'hagan D, Donnelly J, Rappuoli R, Podda A.

    Research Center, Novartis Vaccines, Via Fiorentina 1, 53100 Siena,

    Italy. giuseppe_del_giudice@chiron.com

    "Squalene is a naturally occurring oil which has been used in the development of vaccine adjuvants, such as the oil-in-water emulsion MF59. In past years, by use of noncontrolled and nonvalidated assays, a claim was made that antisqualene antibodies were detectable in the sera of individuals with the so-called Gulf War syndrome. Using a validated enzyme-linked immunosorbent assay for the quantitation of immunoglobulin G (IgG) and IgM antibodies against squalene, we demonstrated that antisqualene antibodies are frequently detectable at very low titers in the sera of subjects who were never immunized with vaccines containing squalene. More importantly, vaccination with a subunit influenza vaccine with the MF59 adjuvant neither induced antisqualene antibodies nor enhanced preexisting antisqualene antibody titers. In conclusion, antisqualene antibodies are not increased by immunization with vaccines with the MF59 adjuvant. These data extend the safety profile of the MF59 emulsion adjuvant."
    ___

    From the pdf doc text:


    http://www.flutrackers.com/forum/att...2&d=1251745072

    ...
    The nonclinical testing of MF59TM consists of research studies
    performed to explore its mechanism of action, ‘adjuvanticity’, and
    ability to enhance protection in challenge models. GLP (Good Laboratory
    Practice) tolerability and toxicology studies have also been
    conducted to fulfil regulatory requirements. Several publications
    describe the enhancement of immunogenicity of a variety of antigens
    adjuvanted with MF59TM in animals [33,28–30,11], whereas
    the results of Novartis’ GLP toxicology studies performed to fulfil
    global health authority requirements for clinical testing or product
    approvals have not been published, to date.

    ___
    ...
    Histopathology
    findings were generally limited to inflammatory responses at the
    injection site. Thesewere of lowseverity andwere partially to fully
    resolved by the end of a 7- to 14-day recovery period. Consistent
    systemic treatment-related findings in animals treated with antigen
    plus MF59TM included increases in fibrinogen levels and slight
    increases in globulin
    . These findings are consistent with administration
    of adjuvanted vaccine formulations.
    ...
    ___
    ...
    To evaluate whether antibodies against squalene are produced,
    an analysis using very sensitive and specific assays, developed at
    theWalter Reed Army Institute of Research, USA [5,35], were used.
    Serum samples taken from individuals before and at various times
    after immunization with MF59TM-adjuvanted influenza vaccine or,
    as a control, with influenza vaccines without adjuvantswere tested.
    The results of these assays show that:
    IgG and IgM antibodies against squalene were detectable at
    very low levels already before immunization with MF59TMadjuvantedinfluenza
    vaccines in the vastmajority of young, adult,
    and elderly individuals
    .
    • Immunization with MF59TM-adjuvanted vaccines did not induce
    any change in the levels of serum anti-squalene antibodies
    .
    • The level of anti-squalene antibodies detectable in the sera of
    subjects immunized with vaccines adjuvanted or not adjuvanted
    with MF59TM was similarly low [36].
    Data obtained with sera fromsubjects fromdifferent geographic
    areas were similar (USA,Western and Eastern Europe) [36].
    Taken together, these data showthat theMF59TM adjuvant squalene
    is not associated with the production of specific antibodies
    (Fig. 2). These antibodies may well represent low-avidity antibodies
    naturally occurring in healthy individuals, and their serum titres
    are not influenced by immunization with MF59TM-adjuvanted vaccines.
    ___
    ...
    Extensive clinical immunogenicity and safety data on various
    MF59TM-adjuvanted vaccine antigens have been generated in
    clinical trials over the last 15 years. The data show that MF59TMadjuvanted
    antigens elicit a strong antibody response, and are safe
    and generally well tolerated [4]. The clinical findings are instrumental
    in the understanding of the adjuvanticity of MF59TM, and
    more importantly of the safety of this compound.
    As an o/w emulsion, the MF59TM adjuvant is very fluid, and
    is expected to be well tolerated and to induce strong short-term
    immune responses as the oil content is very low (between 15 and
    25%
    ) [37]. Furthermore, the route of administration is important as
    it influences local reactogenicity and the immune response.
    Data have been generated across all age groups, including the
    elderly, younger adults, adolescents, and also newborn infants.
    Most experience has been gathered in conjunction with influenza vaccines with more than 14,000 individuals exposed in more than 30 phases 1–4 clinical studies [38,3,39–44]. Before registration in May 1997 Fluad&#174;, had been testedin 28 single- or double-blind,randomized,
    and controlled studies, 13 of which with a 4- to 6-month
    follow-up and 12 studies with a 4-week follow-up.
    24 of 30 studies enrolled elderly subjects (≥65 years).

    Fluad&#174; was tested for equivalence of antigenic content against the inactivated subunit comparator vaccine Agrippal&#174; (same antigenic content as Fluad&#174;, but without MF59TM adjuvant), in 20 studies, against Fluogen&#174;/Fluvirin&#174; in one study, against Fluzone&#174; in two studies, against Influvac&#174; in three studies, and against Flushield&#174; in two studies.
    ___
    ...
    30-26=6 (of 30) = NON-ELDERLY STUDIES)
    ___
    Table 2
    Clinical experience with MF59TM adjuvanted to different vaccine antigens [33]
    Antigen(s) Route of immunization Population Size database (N) Indicationa
    Influenza +MF59TM Intranasally Healthy adults 31 P
    Influenza +MF59TM IM Adults 460 P
    Influenza +MF59TM IM Elderly 11,462
    Influenza vaccine +MF59TM IM Children; adolescents 116 P
    HCVE2 +MF59TM IM Healthy adults 36 P
    Controls: MF59TM + buffer IM Healthy adults 12 P
    HCVE1E2MF59TM IM Healthy adults 48 P
    Controls: saline IM Healthy adults 12 P
    HCVE1E2MF59TM + CpG IM Healthy adults 48 P
    Controls: HCVE1E2MF59TM IM Healthy adults 12 P
    HBV+MF59TM IM Healthy adults 156 P
    HSV-2MF59TM (HSVMF59TM +MTP-PE adjuvant) IM HSV-seronegative and -seropositive
    subjects
    2,422 (104) P
    CMV antigens +MF59TM IM Seronegative volunteers: Incl. 15/500
    toddlers 30/500 seropositive volunteers
    500 P
    Influenza +MF59TM Intranasally Healthy adults 31 P
    Influenza +MF59TM IM Adults 460 P
    Influenza +MF59TM IM Elderly 11,462 P
    Influenza vaccine +MF59TM IM Children; adolescents 116 P
    HBV+MF59TM IM HBV-infected subjects 159 Th
    HBV+MF59TM + Lamivudine IM HBV-infected subjects 120 Th
    Controls: MF59TM + buffer IM HBV-infected subjects 99 Th
    HCVE1E2MF59TM &#177;pegylated Interferon + Ribavirin IM HCV-infected patients 48 Th
    a P = prophylactic; Th = immunotherapeutic
    ...
    5.3.3.6. Influenza vaccine. The US Advisory Committee on Immunization
    Practices produces a regularly updated rationale for
    vaccination against influenza [55]. The current version identifies 12
    categories of patients at high risk of complications from influenza.
    Annual vaccination against influenza is recommended for: (1) all
    persons, including school-aged children, who want to reduce the
    risk of becoming ill with influenza or of transmitting influenza
    to others; (2) all children aged 6–59 months (i.e., 6 months–4
    years); (3) all persons aged >50 years; (4) children and adolescents
    (aged 6months–18 years) receiving long-term aspirin therapy who
    therefore might be at-risk for experiencing Reye syndrome after
    influenza virus infection; (5) women who will be pregnant during
    the influenza season; (6) adults and children who have chronic pulmonary
    (including asthma), cardiovascular (except hypertension),
    renal, hepatic, haematological or metabolic disorders (including
    diabetes mellitus); (7) adults and children who have immunosuppression
    (including immunosuppression caused by medications
    or by human immunodeficiency virus; (8) adults and children
    who have any condition (e.g., cognitive dysfunction, spinal cord
    injuries, seizure disorders, or other neuromuscular disorders) that
    can compromise respiratory function or the handling of respiratory
    secretions or that can increase the risk for aspiration; (9) residents
    of nursing homes and other chronic-care facilities; (10) health-care
    personnel; (11) healthy household contacts (including children)
    and caregivers of children aged <5 years and adults aged >50 years,
    with particular emphasis on vaccinating contacts of children aged
    <6 months; and (12) healthy household contacts (including children)
    and caregivers of persons with medical conditions that put
    them at higher risk for severe complications from influenza.
    There is general agreement on the need to enhance the immunogenicity
    and efficacy of influenza vaccines, especially in adults
    approaching elderly age and in the elderly themselves, when the
    ability of the immune system to mount a strong and efficacious
    response decreases. MF59TM has been proven to strongly enhance
    the immunogenicity in mice, and other small animals, inducing
    antibody titres 5 to >100 times higher than those obtained in the
    absence of adjuvants [56]. Importantly, the enhancement of the
    immune response to an influenza subunit vaccine, mixed with
    MF59TM, was not affected by pre-existing immunity to the virus
    [57]. This observation is particularly important because immunization
    against influenza is routinely carried out every year and
    pre-existing immunity can negatively affect the efficacy of subsequent
    immunizations. In preclinical studies, MF59TM adjuvant
    offered improved protection against influenza virus challenge and
    significantly reduced the viral load in the lungs of challenged mice
    [58]. Clinical trials of the MF59TM-adjuvanted influenza vaccine are
    summarized in Table 2.

    ___
    ...
    3216 V. Schultze et al. / Vaccine 26 (2008) 3209–3222
    5.3.4. Special populations
    5.3.4.1. Adults (non-elderly).
    The overall database consists of 460 subjects aged 18–64 years who have received at least one immunization with Fluad&#174;; 104 of these subjects also received a second immunization.
    The pooled analysis includes data from 460 subjects vaccinated with Fluad&#174; and 453 subjects vaccinated with comparator vaccines (Agrippal&#174;, Fluzone&#174. Overall, these data show that post-immunization reactions, particularly local reactions, were more frequent in non-elderly adults than in elderly
    subjects.
    Compared to unadjuvanted vaccines, Fluad&#174; induced
    more local reactions, most of which, however, were mild and of
    short duration
    . In the Fluad&#174; group after the first injection pain
    was rated mild to moderate in 87%, 10% had none and 3% of subjects
    had severe pain; after the second injection pain was rated
    mild to moderate in 83%, 16% had no pain, and 1% had severe
    pain.
    A statistically significant increase in the incidence of injection
    site—warmth, chills, myalgia, and analgesic/antipyretic use,
    occurred in the Fluad&#174; group after the first injection, but not after
    the second
    . No longer lasting reactions were noted [38].
    5.3.4.2. Elderly subjects. The overall database for safety of Fluad&#174; and Fluad&#174;-like vaccines consists of 11,462 elderly subjects (≥65 years of age) who received at least one immunization with Fluad&#174;.
    The comparator vaccine group includes 6216 subjects who have
    received at least one dose of licensed comparator vaccine (e.g.,
    Flushield&#174;, Fluvirin&#174;, Influvac&#174;, Vaxigrip&#174.
    Immunization against influenza is normally administered every
    year due to the antigenic variability of the viruses responsible
    for seasonal epidemics. Therefore, the evaluation of a potential
    increased reactogenicity associated with repeated immunizations
    was part of this clinical program.
    This aspect is even more relevant
    for Fluad&#174;, since it contains MF59TM inducing a higher incidence
    of mild and transient local reactions
    compared to unadjuvanted
    vaccines.

    For this reason, several trials of this clinical program were
    ‘extended’ to the following influenza seasons to evaluate the safety
    of a second and a third immunization with Fluad&#174;.

    These data indicate that multiple immunizations (up to three)
    with Fluad&#174; were well tolerated (Table 3). Subjects enrolled in second
    and third immunization trials were predominantly those who
    did not experience local reactions to the first immunization.
    An
    ad hoc analysis showed that demographic characteristics and incidence
    of reactions in subjectswithdrawing from the first trialwere
    not different from those of subjects included in the extension trials.
    One phase 4, single-blind, randomized study to evaluate the
    safety and effectiveness of Fluad&#174; versus a licensed influenza vaccine
    (Influvac&#174 administered to elderly (≥65 years of age) subjects
    enrolled a total of 9194 subjects to receive Fluad&#174; vaccine, and 4550 subjects enrolled to receive the control vaccine (Influvac&#174.
    A total of 750 serious adverse events were observed in the Fluad&#174; group (i.e., 8.2%) versus 386 in the control (Influvac&#174 group (i.e., 8.5%).
    The rates of adverse events requiring a physician visit with onset
    between days 0 and 6 and of serious adverse events during the
    study period (October 1997 to April 1998) were low and similar to
    the non-adjuvanted control vaccine Influvac&#174;. Hospitalizations and
    deaths during local influenza season period (24 December 1997 to 4
    May 1998)were similar to the control vaccine. One SAEwas considered
    possibly related to Fluad&#174;. From this finding it can be derived
    that for Fluad&#174; the incidence rate of such AEs (i.e., both serious and
    possibly related) in the entire population does not exceed 0.05% (or
    1 in 1933 subjects).
    In the entire clinical database, only 3 SAEs were considered by
    the investigator to be related (exudative erythemamultiforme, Herpes
    Zoster, pancreatitis and cholangitis) to immunization [33].
    5.3.5. Other routes of administration of influenza vaccine
    The MF59TM-adjuvanted influenza vaccine was given
    intranasally to 31 subjects in a phase 1 study of healthy adults.
    The safety and immunogenicity was compared to unadjuvanted
    influenza vaccine (Agrippal&#174; and placebo). Neither local (sneezing,
    unpleasant taste, bloody nasal discharge) nor systemic reactions
    differed significantly between the treatment groups. No SAEs
    occurred in this study [59].
    5.3.6. Pediatric immunization
    Until recently, influenza vaccination in children was recommended
    only for individuals with medical conditions that could
    put them at higher risk from influenza infection, such as bronchial
    asthma. The Advisory Committee on Immunization Practices (ACIP)
    of the Centers for Disease Control and Prevention recommended
    use of trivalent inactivated influenza vaccine in all children 6–23
    months old, including healthy children with no chronic medical
    condition, beginning in the winter season of 2004–2005 based
    on increasing evidence of high morbidity from influenza infection
    in young children [60]. An increasing number of children in
    the United States are being vaccinated [61]. To achieve the goal
    of universal influenza immunization coverage for healthy children,
    health care professionals will need a greater understanding of
    the severity of influenza illness in this age group, coupled with
    an increased knowledge of indications for vaccine administration.
    One pediatric trial has compared the safety and immunogenicity
    of Fluad&#174; and unadjuvanted vaccines (Fluogen&#174;, Flushield&#174,
    in children and adolescents. In this study, performed in the USA,
    Fluad&#174; was compared to two other influenza vaccines licensed in
    the USA. A total of 116 subjects (9- to 17-year-olds)were vaccinated with Fluad&#174; and 100 subjects were vaccinated with comparator vaccines. The safety profile emerging from this trial was similar to that of older age groups with a moderately increased rate of pain, chills, malaise and headache in the Fluad&#174; group.

    A second randomized, observer-blind pediatric trial in children
    recently conducted in Finland [62] compared safety and immunogenicity of Fluad&#174; to a conventional Influenza split vaccine. A total of 130 healthy children (6–59 months of age) received 2 doses of Fluad&#174;. As with other clinical trials, local and systemic reactions were recorded for 7 days after each immunization, and all other AEs recorded throughout the entire study period with a followup period of 6 months. Both vaccines were equally well tolerated except for injection site swelling which was higher in the Fluad&#174; recipients.
    A third clinical study in children is ongoing to investigate safety
    and immunogenicity of amonovalent influenza vaccine, containing
    H5N1 antigen with MF59TM adjuvant [33].

    However, these clinical data are too limited to draw final conclusions
    on the pediatric indication of Fluad&#174;, which will require
    more extensive clinical investigation.
    ...
    ___
    5.4. Postmarketing experience
    The favourable safety data demonstrated in clinical trials are
    supported by postmarketing pharmacovigilance since first registration of Fluad&#174; in September 1997.

    Meanwhile, more than 27 million patients have received
    Fluad&#174; (or Fluad&#174;-like vaccines
    sold with other brand names
    such as Adiugrip&#174;, Addigrip&#174;, Prodigrip&#174;, Influpozzi&#174; Adiuvato,
    Gripguard&#174;, Chiromas&#174 during the past 9 years, most of which
    were administered to the elderly.

    Fluad&#174; is only licensed in the elderly, and a separate safety evaluation in children will be required, once the target population of
    immunization can be extended to children.
    Reports on suspected spontaneous ADRs after immunization
    with Fluad&#174; are collected on an ongoing basis.
    The Fluad&#174; pharmacovigilance database involves all individual
    ADR case reports, regardless of their causality. All reports from
    September 1997 (when Fluad&#174; was first marketed) to August 2006
    (before start of the 2006 influenza season) were included in this
    analysis. In order to ensure coherence and analysis of reported
    events, all were classified according to MedDRA.
    ...
    ___

    (ADVERSE EVENT)

    Atotal of 57%of case reportswere fromelderly vaccine recipients
    whowere 65 years or older, which is the target group for immunization
    (Fig. 4). Another 34% of cases were from adults (18–64 years),
    1% of cases were from adolescents and children
    , and 8% were cases
    of unreported age.
    ...
    5.4.1. Serious cases
    In total, 107 cases met at least one seriousness criterion, most
    often (64.8%) “hospitalization”, resulting in a reporting rate of 0.39
    serious cases per 100,000 doses sold
    . Of these, 34 cases were consideredpossibly
    relateddue to temporal or biological plausibility, or
    both, according to the company internal causality assessment. The
    AEs reported in these serious cases belonged to a variety of clinical
    entities.Most frequently reportedAEswere injection-site reactions,
    skin reactions and subcutaneous tissue disorders, neurological disorders
    (myelitis (n = 1), transverse myelitis (n = 1), Guillain-Barre&#180;
    syndrome (GBS) (n = 6), Personage Turner Syndrome (n = 1)), and
    respiratory symptoms. No new or uncommon trend of AEs
    (compared
    with company internal data on other influenza vaccines, like
    Agrippal&#174;, Begrivac&#174;, and Fluvirin&#174 or any signs of increased frequency
    of listed AEs have been identified.
    5.4.2. Fatal cases
    During the evaluation period, 13 cases of death in elderly
    patients, 68–91 years of age, were reported after use of Fluad&#174;.
    None of the death cases occurred in persons below 65 years of
    age.

    ...

    Leave a comment:


  • sharon sanders
    replied
    Re: Swine flu vaccines, adjuvants, equity, safety

    Swine flu vaccines, adjuvants, equity, safety: more discussion

    Category: Infectious diseaseInfluenza treatmentPandemic preparednessSwine fluVaccines
    Posted on: September 8, 2009 6:15 AM, by revere


    As we expected, yesterday's vaccine piece provoked a lot of discussion, almost all of it thoughtful and pertinent. Since we've already said we might be wrong, we thought we'd take some time to respond, using it as a way to keep thinking things through on our end. Writing is thinking and thinking is needed in this situation.


    Over at FluTrackers.com (an excellent flu forum like Flu Wiki with highly informed people) there were a number of lengthy responses, most of them on the negative side. Since these folks follow events closely their opinions are also worth following closely. In addressing them I will also summarize the gist of yesterday's post, which represents the Reveres' joint opinion at this point.


    1. We have been somewhat skeptical of the efficacy of influenza vaccination in the past. However reviewing the literature (we dealt with a good summary in this post recently) we have come to the conclusion that the vaccine works sufficiently that it is an important public health measure. Its efficacy varies but, depending upon the group, probably lies somewhere between 30% and 70%. In the case of a good match to a virus to which most of the population has no natural immunity, we believe 70% to be a good estimate considering the groups most at risk. This means that compared to an unvaccinated group, the vaccinated group will have 70% fewer infections. It means that 30% of those vaccinated who are exposed will still get the flu. Flu vaccine isn't even close to 100% effective like DPT or MMR. But even 30% reduction in infection in a pandemic is a Big Deal in terms of demands on services, lost work time and productivity, pain and suffering, and of course, mortality, so we don't think using the high end of efficacy makes much difference.


    So that's the first point that may separate us from others. We think the vaccine will work and we base that on experience with seasonal vaccine where numerous randomized clinical trials have been done (see the Basta-Halloran review we linked above; here it is again). Take a look at it and make up your own mind about this. If you don't think the vaccine will work, then there's no reason to get it. We think it will work (based on our review of the science) and that it will make a big difference to how well communities who use it sufficiently will get through whatever might come next.


    2. Safety, adjuvanted or unadjuvanted. Yesterday's post pointed out that it is not feasible to assure the advance safety of any product being consumed or administered to tens or hundreds of millions of people. No advance testing is possible for relatively rare adverse events that would still be numerous when that many people are exposed. But the mathematics of the adverse events versus the risks from flu, even if it is only the virulence of seasonal flu, is so overwhelmingly in favor of vaccination that we don't think this is a hard call. True, there are various guesses that have to be made about how many people are infected, what the CFR will be, how well the vaccine will work, etc., and while we tried to be pretty conservative in most of them (we did use a high end number for vaccine efficacy because we thought the data for similarly placed populations merited it, but even if we'd used the lowest efficacy vaccines come out far ahead), and you might differ with some of them. At least you know what we assumed. But the major point is this. If you want to wait for assurances of safety, then you better have a definition of "safety" that is determinable ahead of time or you are just saying you won't accept any vaccine. And for most of the rare events people talk about (e.g., Guillian-Barre Syndrome) there is no way to test for it in advance.



    A related point was that there is no reason to trust vaccine manufacturers as they have a dismal record for honesty and probity. We agree and have complained bietterly about Big Pharma many times. But accepting this argument also means we reject essentially the entire modern pharmacopoeia since these folks also make all the other vaccines, antibiotics, hand sanitizers, etc., etc. We've argued frequently that influenza vaccines (and probably other vaccines) should be made by a regionalized network of international vaccine institutes outside the market system. We didn't do that. So we are stuck with Big Pharma. It is what it is.


    3. The adjuvant question. Two weighty objections to our advocacy of adjuvants have been advanced, one at FluTrackers and one by Jody Lanard here. They are slightly different but we will take them together. Vibrant62 at FluTrackers observes that the safety of adjuvants has been tested more often in the older age groups (where the immune response is more sluggish and adjuvants are more needed), not well tested in the young age groups. Vibrant62 suggests the decision doesn't have to be "all or nothing" but we could use unadjuvanted vaccine for some age groups (or pregnant women) and adjuvanted vaccine for others. Let's assume this is economically feasible (i.e., that two different vaccine could be made and distributed efficiently). If children and young adults really, on average, react quite differently to a particular adjuvant, then this will be seen in the safety and efficacy trials, unless it is rare, in which case we are in the same box we were earlier regarding trade-off with the benefit. There has been quite a lot of experience with adjuvants and influenza virus and also some with this particular virus. I will refer you to the excellent post by Vincent Racaniello at Virology Blog. Before giving my full answer to this, though, I want to address Jody Lanard's objections, since my answer is the same to both.


    Jody Lanard and Peter Sandman are among the most experienced and thoughtful practitioners of risk communication anywhere, so their views are of special significance. We usually agree, although not always. This seems to be one of the "not always" times. Jody's concern has to do with how the US public will react to the idea that a relatively untested vaccine will contain an even more untested additive, especially after the 1976 swine flu debacle where it is widely reported that the vaccine was worse than the disease (although not reported that one reason this is so is that the disease never got out of Fort Dix so there was no disease averted by the vaccine). This comes at a time of high anxiety about vaccines among certain segments of the population, some of it sincere, much of it fed by paranoid conspiracy theorists who see monsters under every bed. The bad behavior of Big Pharma and the demonizing by the Far Right Noise Machine of any health measure promoted by government adds to the problem. The result is that the anti-vaxxer movement is killing and disabling children. The fear is that a government program with an adjuvanted vaccine will pour gasoline on this fire:
    There is a great deal of undue -- but thoroughly unmitigated -- anti-vaccine feeling and fear in the U.S. The anti-vaccine activists and the vaccine-causes-autism activists are ready to roll with every flu vaccine Teachable Moment that comes along. The more traction they can get by encouraging doubt and skepticism about flu vaccine among parents, the more children will end up unvaccinated against the "usual" childhood diseases. So in the U.S., this is a really bad time to change the flu vaccine any more than necessary (a strain change is necessary, of course). (Jody Lanard in the Comment Thread of yesterday's post)
    In essence (and read the whole comment here), Dr. Lanard is saying it will backfire and make things worse. Instead of more people being vaccinated because of antigen sparing, fewer in the US will be vaccinated because parents will refuse the vaccine and it will have a spillover effect on other important childhood vaccination programs.


    I understand this point of view and it comes from what I consider an authoritative source. But here's where the question of "balance" that I discussed in yesterday's post comes in. Jody and I have struck different balances on this. For us, the principal point of using adjuvant is to increase the number of people in the world who can be vaccinated, not just the number of people in the United States. Most of the viral antigen is made outside the US. We are rich so we bought it up and now less rich countries can't get it. Our only entitlement to it is through the fact that the ability to live without influenza infection has become a commodity and the US has the means of exchange (money) to buy it. Adjuvants would make it more available to more people.


    I am opposed to mandatory vaccination, even though I believe vaccination is an important public health measure that will save millions of lives. But there isn't enough vaccine for everyone in the world, so if people in the US don't want it, then any unused stock (keeping a small reserve) should be released by a date certain (say January 15 for the sake of argument) and given to others. I believe this will doom many Americans to severe sickness and some to a fatal illness, but the compensation is that many others, children and adults, in poorer parts of the world will be saved. Their lives are worth no less than American lives. If someone in this country, for whatever reasons, doesn't wish to receive the vaccine, someone who wants it and needs it will be waiting.


    There are real imponderables and trade-offs here with no easy answers. It is clear that our answer is not the same as others who have followed the issue as assiduously as we have and who have great expertise. That doesn't make them right, or us right, or the US government's position right. And different governments are making different decisions. We may never know what the right thing to do was because we will be dealing with a counterfactual: what would the world have been like if we'd done X instead of Y?


    But the US is a big player in this high stakes game. It has ordered (and hence pre-empted for others) a lot of antigen, so it's something worth discussing. So we're discussing it.

    Leave a comment:


  • Vibrant62
    replied
    Re: Swine flu vaccines, adjuvants, equity, safety

    Because of the changing nature of viruses, and the rapidity by which a 'new' product must be made annually, the fact remains (and is likely to remain) that the burden of proof for safety testing for influenza vaccines is far lighter than any other area of pharmaceutical medicine. It is no good to have to undergo year long safety evaluations, when by the time they were completed, the nature of the virus and vaccine will have fundamentally changed. Adjuvant use was not extensively considered until the world faced an imminent H5N1 pandemic, and as a consequence, in my opinion, thier use and the evaluation of their use has been rushed. We may not have time to answer these questions in a hurry, right now - but even if corners are cut NOW, then manufacturers should still undertake full safety testing of adjuvants as soon as possible to guide future decisions. this is not the last pandemic situation we will face.

    Adjuvant safety testing has been restricted to its use in association with specific vaccines. To echo Tropical's comments I would like to see globally applicable, full safety testing and clinical trials of adjuvant given ALONE and in isolation as well as with specific vaccines, with a longer term ADR follow up than the 7 day (or at maximum 30 day) standard that it applied wjhen it is used with influenza vaccines. This would help to answer the basecase inherent safety questions of adjuvant use. As far as I have been able to discover, this has never been done.

    Such testing then needs to be followed up by widespread trials of adjuvanted influenza vaccine using age specific groups and including target vaccine populations i.e those with underlying health conditions.

    It will be impossible to carry out such testing with every influenza vaccine in view of its changeability and costs - but it would make current levels of testing more adequate, if each adjuvant has at least been properly and thoroughly investigated as a single entity. As to why the EU has seen fit to approve these vaccines and the US has not, all I would say is that IMHO 'the hurdle' for proof of efficacy and safety has been set at a very low level in the EU, and US requirements are more stringent. I find it a cause for concern that the US should be considering lowering its standards to accomodate adjuvant vaccines - and if it does so, I hope it is temporary and with long term conditions applied, so that the current emergency situation can be met.

    the probability is that adjuvants will be both safe and effective for the vast majority. the point of such detailed safety testing should be to throw up which population groups should be contra-indicated, and which practices (such as multiple anitgenic challenges, perhpas) should be avoided. Even if the powers that be decide that the world cannot afford to wait for answers to these questions now, it is important that manufacturers should not be exempted from investigating throroughly (i.e include up to one year's follow up looking for ADRs) in the future.

    Leave a comment:


  • FloridaMom
    replied
    Re: Swine flu vaccines, adjuvants, equity, safety

    When my now-10 year old was 7 weeks old, the pediatrician called me and told me that she was seeing many cases of rotavirus in her patients and recommended that I give my son the rotavirus vaccine. Although he and my other children had always been given every vaccine that was recommended, I had a "funny feeling" about this one (mother's instinct). I placed a call to the CDC to see if there had been any harmful reactions to the vaccine in newborns and spoke to a doctor who was very reassuring and told me I had nothing to fear. My child had the vaccine, and as a result was hospitalized with bloody, awful diarrhea that was attributed to the vaccine. He recovered, thank God, but several months later the vaccine was pulled because of the many adverse reactions, including death, in young children. This vaccine obviously was not tested well enough, or IMHO, children wouldn't have died.

    Now, again, I'm being told a vaccine is "safe" although it clearly is being rushed through testing, and the drug compainies are told they will not be held liable if anything goes wrong. (So where is the motivation to test well? If they test *too* well, they might discover something bad, so better not to do that, right?)

    As much as this flu scares me, I would in no way feel comfortable allowing my children to be guinea pigs with this vaccine. I wish we had PROOF of the safety of the vaccine, but that won't happen, or the drug companies would not have been given immunity.

    Just my 2 cents!

    Leave a comment:


  • Snowy Owl
    replied
    Re: Swine flu vaccines, adjuvants, equity, safety

    Canada to buy unadjuvanted vaccine for pregnant women, health officer says
    By Helen Branswell Medical Reporter (CP) –


    TORONTO — Canada will purchase supplies of unadjuvanted swine flu vaccine to offer to pregnant women who might otherwise choose not to be vaccinated, the country's chief public health officer has revealed.

    Dr. David Butler-Jones told The Canadian Press that Canada will buy 1.2 million doses of unadjuvanted pandemic vaccine which will be reserved for pregnant women, who are at significantly greater risk of becoming severely ill and dying if they contract the virus.
    "I'm anticipating for pregnant women we will have an option," he said in an interview.

    The vaccine will be supplied by GlaxoSmithKline, Canada's pandemic vaccine manufacturer, and is expected to be available at the same time as the country's other supplies of vaccine.

    Adjuvants are compounds that boost the immune system's response to vaccine, allowing smaller doses to be used per person. Canada is buying adjuvanted pandemic vaccine partly in response to a call from the World Health Organization for affluent countries to use "antigen (vaccine) sparing" techniques so that limited global supplies can be stretched as far as possible.

    While some European countries have used adjuvanted flu vaccines for a number of years, none of the currently licensed flu vaccines in Canada contains an adjuvant.

    And there are no data on the use of adjuvanted flu vaccine in pregnant women - a fact that may add to the already high degree of reluctance many pregnant women feel about taking any medication or therapy.

    "What is absolutely clear is that there is much more of a safety data base in pregnant woman with non-adjuvanted vaccine," said Dr. Marie-Paule Kieny, head of the WHO's vaccine research initiative, the division overseeing pandemic vaccine issues.
    "Does it mean that it (adjuvanted vaccine) will be unsafe? No. It means that there is no hard evidence that it will be (safe)."


    The lack of evidence led a panel of experts that advises the WHO on vaccine issues to recommend unadjuvanted vaccine be offered to pregnant women if that option is available.

    Leave a comment:


  • tropical
    replied
    Re: Swine flu vaccines, adjuvants, equity, safety

    Dificult evaluation.

    I think many have in family, or knows persons who are flu susceptible and at the same time have many chronic illness at once.

    Some heart patients are on risk of severe illness and death from sesonal flu also, and thus they must vaccinate themself.
    Similar need have the lung/.../ or dialised patients.

    It was reported by news text about people having lung, renal or heart conditions, constricted on vents or even died because of this pandemic.

    The above facts can't be ignored, and because of vaccine lack, and vaccine under-production of the corporations which don't enlarge the production lines in time, now the adjuvant options entered.

    The same moment when unisonic - the WHO, and all of the countries, by rejecting previous suggestions of posponing the schools/Univers. openings, or made strict closures at the first several infected scholars (leaved the decisions to indiv. countries).

    By doing so, they push faster us all into the vaccination/adjuvant or non/ decision, for the risk groups especialy, but other more sane also.


    One thing seems to me that screaming at the world level -
    the inability of the world scientific community, and the vertic suggestion health body (WHO), to made a clear scientific singular statement about:
    WHY it was possible to regulatory allow the usage of one adjuvant (MF59) in one part of the world (EU/...), and at the same time scientificaly discarded it in other world countries (USA/...), all based on scientific results?

    The result can be only one everywhere, if it is scientific proven.

    Science is so proud of it's repetitivity when make sci. claims, and decisions to follow.

    So, if it is scientificaly proved good for EU/... regulation processes to allow the use of MF59 - the only stated long used before, than it must be the same scientificaly good for all (US/...world) regulators, or it must be no good for both.

    If the WHO, or an scientific vertics world body of scientists, now evaluate that MF59 is safe to be used (even in some groups only), than it must be good and safe used in all humankind countries worldwide.
    If it is proved that it is not good, than it must be banned everywhere.

    But there will be no half measures scientists decisions - they must decide - not leave it on us, and tolerate changes of laws which could allow harmfull things on the field.

    Several other questions:

    #12:
    "Regulators face tough flu-jab choices
    Rich countries' pandemic strategies may cause vaccine shortages elsewhere."

    #11:
    "However, this is a fastracked vaccine developed for a catastrophic scenario being applied to a relatively mild virus. Its a dream opportunity for the pharmaceutical companies to mass trial their novel agents with little risk of litigation. It makes me uneasy. If this was H5N1 it would be a different risk/benefit analysis. But injecting relatively untested agents into the immune system of a child; not happening."

    #10:
    "Until there is robust safety data I too would elect to go for the Baxter vaccine - but as stated for certain population groups (age 65+), I expect the risks are low and that vaccines with such adjuvants have thier place and thier benefits. On the basis of the risk - benefit equation, I would not advocate"

    #9:
    "Unlike Novartis' squalene-based MF59, AS03 is relatively new and has not been used as extensively. Call me stupid, but I think here in the UK i would rather go for Baxter's unadjuvanted H1N1 vaccine. (Although I am intrigued about protection from antigenic-drift offered by adjuvants.)

    There is still a lot of claim and counter-claim on the web regarding squalene and gulf war syndrome. I would be interested in anyone's views."
    An recent FT posted study (excerpted) claim that by standard guideliness proper procedures used and conducted to asses such claim, such squalene link with gw syndrome is not established.

    It's the researchers/WHO part, to dismiss or not, such claims which now could represent a reason to not be inoculated if demonstrated, or the oposite.

    #8:
    "...
    WHO recommends that health workers be the first, to protect the health system and allow them to care for influenza and other patients. The strategy a country takes will depend on its policy objectives and the availability of vaccine.
    ...
    Q: WHO has recommended the use of adjuvant in pandemic vaccines, but some countries don’t plan to follow this guidance.

    A: Many countries, including the USA, have not licensed vaccines with adjuvants of any kind yet. Other vaccines with the same type of adjuvant as planned for pandemic influenza A (H1N1) vaccines have, however, been licensed in European countries. Countries that intend to use vaccine with adjuvant will find that there is a large body of safety data for adults and some for children. In any case, all countries will need to carry out good post-marketing surveillance to make sure that they pick up any early sign of a safety problem with a particular vaccine.
    ...A complete clinical evaluation is not needed also because manufacturers produce seasonal influenza vaccines using the same procedure and equipment, but for a different virus each year. In the USA, vaccines for seasonal influenza are licensed without clinical trials on the basis of a “strain change”.
    ...
    In Europe, a strain change is accompanied by a small clinical trial requested by the European Medicines Agency.
    ... they can use the same procedure to make H1N1 pandemic vaccine. That way they can get a licence in a few days. This is another way vaccines can be licensed without clinical trials, while still ensuring safety on the basis of what is known about influenza vaccines.
    ...
    There are other measures, such as social distancing, school closure, avoidance of large gatherings, antibiotics and personal hygiene.
    ...
    there is just not enough vaccine for every country in the world to vaccinate every member of the population twice."
    Than - WHO must not suggest schools openings, free gatherings and free traveling in hotzones, but the oposite: closures, and restrictions.

    Because of free roaming advisories now the question circled about not enaugh vaccines, and not in time, or adjuvants needed, instead to have additional several months to augment the vaccines quantities.


    #6:
    Please voice your opinions.


    #5:
    "I'm a bit gun shy after my bad experience with a seasonal vax and a bad doctor.
    I still get seasonal flu jabs, but only use the visiting nurse service or get the shot in my doctors office (different doc, of course).

    On top of my concern over the true safety of the vaccine, whether or not it contains adjuvants, I'm not entirely sure how much protection it would provide.
    My husband and I have both been sick multiple times this summer and know many others who seem to be experiencing the same thing.
    While none of us has been tested or confirmed to have H1N1, given the symptoms, it's the most likely scenario.

    If we continue to contract it, over and over again, after having had it - how much more protection would an iffy vaccine provide?"
    The vaccine administration must not be leaved to not trained staff.

    Bulk doses delivered vaccines could make more problems of adverse effects if remained open more time than several minutes, so make one-dose-ready vaccines. Don't spare on others neck - introduce an individualy payed 1additional ticket if it is necessary to pay more.

    If it will be repetitive, we will have big problems, but at least we will try to shield us.

    #4:
    "But for all of those who knows how to avert or treat an infection and taking into considerations their environment (arsenic, nitrites, etc..) the climate, the social mood and their access to alternatives options should back off and wait until spring if possible.
    ...
    Gov get into nuclear reactors to check if everything is ok why dont they do the same thing with big pharma? "
    Unfortunately, it seems that to avert enaugh the pandemic, because of so much toxicals and other diferences, it could be also a risk to not be (safely) vaccinated, for many patients with various joined illness present.

    About the checkings, it is realy a failure if the gov. safety check hand can't check any item which will affect the taxpayer population in any way, especialy if claimed as an shielding safe vaccine.
    The insertion of production corp. shielding must not negate the gov evaluation, or produced more harming products without other safe shielding options on the field for the endangered population.

    #3:
    "why a proportionate use selected by age group cannot go ahead now, with reservations for children and young adults until we have definite answers from proper clincial trial work.

    The virus is likely to change before this pandemic is over. We may need to repeat the vaccinations we are planning now to counter a mutated or changed virus, that could well be more severe. We need these answers to make proper plans for the future - and if necessary select population groups for whom adjuvanted vaccines may be inadvisable, leaving adjuvant vaccines available for the vast majority and freeing up resources for more peoples of the world - safely."
    Good possibility, but the researchers must fast exit the diatribes and made an joint statement about, especialy the WHO which "suggestions" must became exact guideliness.

    #1:
    "There are a lot of other balance issues here, including one raised by WHO's vaccine chief Dr. Marie-Paule Kieny. If the swine flu virus drifts genetically, those getting an adjuvanted vaccine may be at an advantage."
    WHO, knowing the above drifted virus adjuvant protection, must assure a fast global world scientific singular only answer about adjuvant MF59 at least, or even others adjuvant safety for people usage.

    #1, Link1:
    link2:
    http://www.virology.ws/2009/09/01/ad...-h1n1-vaccine/

    "I know that many readers are concerned about the possible side effects of adjuvants. MF59 has been used for 12 years in seasonal influenza vaccines in Europe and is considered a safe adjuvant. However, the Centers for Disease Control and Prevention believes that the 2009 H1N1 vaccine will likely not be used with adjuvant.

    Dormitzer, PR, Rappuoli, R, Casini, F, Wack, A et al (2009). Adjuvant is necessary for a robust immune response to a single dose of H1N1 pandemic flu vaccine in mice PLoS Currents: Influenza"
    It must be conducted one scientifical global world result, and fast evaluated the problem of the several years used MF59 - safe, or not,
    or at least (as above suggested by a poster) safe for which groups of people.

    Leave a comment:


  • Sally Furniss
    replied
    Re: Swine flu vaccines, adjuvants, equity, safety

    July 21, 2009

    Regulators face tough flu-jab choices
    Rich countries' pandemic strategies may cause vaccine shortages elsewhere.

    by Declan D Butler
    Nature News

    ...The United States' global responsibility to consider dose-sparing strategies is briefly alluded to in the minutes of a mid-June US National Bio*defense Science Board meeting, released on 17 July: "Federal decision-making will affect not only the 300 million Americans who depend on the government to support the public health system but also people all around the world."

    The United States has certainly kept open the option of using adjuvants. It has already allocated almost US$2 billion for antigen and adjuvant to provide every American with up to two doses of vaccine. That sum includes orders of $483 million for Novartis's MF59 adjuvant, and $215 million for GlaxoSmithKline's AS03 adjuvant. ......

    http://www.bioedonline.org/news/news.cfm?art=5474

    Leave a comment:


  • hermit
    replied
    Re: Swine flu vaccines, adjuvants, equity, safety

    I concur with your conclusions Vibrant62. Its one thing to take a (all be it small) risk with one's own health, but I would not be prepared to have my 3 year-old's long term health put at risk by a novel adjuvant. I am not one of the many anti-vaccine reactionaries that inhabit flublogia, my child has had the full UK infant vaccination program (a not inconsiderable number of jabs) and seems to be totally fine and in rude health. However, this is a fastracked vaccine developed for a catastrophic scenario being applied to a relatively mild virus. Its a dream opportunity for the pharmaceutical companies to mass trial their novel agents with little risk of litigation. It makes me uneasy. If this was H5N1 it would be a different risk/benefit analysis. But injecting relatively untested agents into the immune system of a child; not happening.

    The same applies to the Gardasil vs Cervarix decision when that eventually arises.

    On a different point I am concerned at the disparity between the vaccine priority groups advocated in the UK compared to elsewhere. Healthy children are not a priority here, unlike the US. My child has started preschool, and I know that in the absence of vaccination she will get flu, its just a matter of time. It is a worry .

    Leave a comment:


  • Vibrant62
    replied
    Re: Swine flu vaccines, adjuvants, equity, safety

    Without proper, well constructed trials, there will be no answers. Gulf war syndrome is likely to be multifactorial but I am not persuaded that squalene had no role to play. If you dont look you don't find, in this case I think.

    Until there is robust safety data I too would elect to go for the Baxter vaccine - but as stated for certain population groups (age 65+), I expect the risks are low and that vaccines with such adjuvants have thier place and thier benefits. On the basis of the risk - benefit equation, I would not advocate that mychildren had it though unitl there is evidence to show that it is safe, with THIS virus. if we were facing an H5N1 pandemic my answer might well be different, as the risk - benefit equation would be wholly different.

    Leave a comment:


  • hermit
    replied
    Re: Swine flu vaccines, adjuvants, equity, safety

    Glaxo's anti-HPV vaccine, Cervarix, uses AS04 as its adjuvant. I don't believe this contains squalene. For its upcoming pandemic H1N1 vaccine, Glaxo will be using its novel squalene-based adjuvant, AS03. Unlike Novartis' squalene-based MF59, AS03 is relatively new and has not been used as extensively. Call me stupid, but I think here in the UK i would rather go for Baxter's unadjuvanted H1N1 vaccine. (Although I am intrigued about protection from antigenic-drift offered by adjuvants.)

    There is still a lot of claim and counter-claim on the web regarding squalene and gulf war syndrome. I would be interested in anyone's views.

    hermit

    Leave a comment:


  • Snowy Owl
    replied
    Re: Swine flu vaccines, adjuvants, equity, safety

    WHO Position

    WHO supports fair access to influenza A (H1N1) vaccine. An interview with Marie-Paule Kieny

    <table class="bgbx"><tbody><tr><td class="bx7">
    <table width="144" align="left" border="0" cellpadding="0" cellspacing="0"> <tbody><tr> <td class="ileft">
    WHO/L Solberg
    Dr Marie-Paule Kieny
    </td> </tr> </tbody></table> Dr Marie-Paule Kieny is director of the Initiative for Vaccine Research at the World Health Organization (WHO). She received a degree in Economics in 1977, followed by a PhD in microbiology in 1980, both from the University of Montpellier in France. Her research career began with the development of a recombinant rabies vaccine. Since then, she has worked on the design of AIDS vaccine candidates and done research on cancer immuno-gene therapy, targeting mainly breast and cervical cancers. She has also served on several expert committees on vaccine discovery, AIDS and cancer research.


    </td> </tr></tbody></table> The vast majority of cases of pandemic influenza A (H1N1) have been mild so far with few deaths. It remains to be seen whether the virus will mutate into a more virulent strain. Marie-Paule Kieny explains how WHO is supporting countries’ efforts to protect their populations with vaccines that should become available as of this month.



    Q: When will the first doses of vaccine for the pandemic influenza A (H1N1) be ready?

    A: Some manufacturers announced in July that vaccine is available, but that doesn’t mean it’s ready for use, as it needs regulatory approval. Regulatory authorities are considering the best way to register these vaccines as quickly as possible. The consensus is that the first doses will be available to governments for use in September.


    Q: Who will get vaccinated first? Who decides this?

    A: Vaccine will not be available on the private market and governments will decide who gets vaccinated first. WHO recommends that health workers be the first, to protect the health system and allow them to care for influenza and other patients. The strategy a country takes will depend on its policy objectives and the availability of vaccine.



    For example, if a country decides to concentrate on protecting essential infrastructure, it may target different people, such as truck drivers, if they are critical for food delivery. Others may try to reduce transmission of the virus. For example, the United States of America decided to immunize children before or at school entry who are in closer physical contact than adults and can amplify infection rates. Countries may also try to reduce morbidity and mortality and target specific groups, such as pregnant women. Some high-income countries have ordered enough vaccine for the whole population. Nevertheless, no countries will have vaccine for everyone from the first day it is available for use, so that each country will need to prioritize. Some middle-income countries have also placed contracts with pharmaceutical companies and have been purchasing vaccine for between 1% and 10–20% of the population.



    WHO is working hard with manufacturers, governments and donors to ensure that developing countries can access vaccine as soon as possible to immunize their health workers, and when more vaccine becomes available, other groups will be immunized.


    Q: How are influenza vaccines produced?

    A: The main method is by injecting seed virus into embryonic chicken eggs and harvesting the fluid after several days and purifying it. There are two technologies. More than 90% of influenza vaccines available are known as “inactivated vaccines”, which means you kill the virus to produce the vaccine. Less common are “live attenuated vaccines”, which are derived from a weakened form of the virus that is not killed.


    Q: How many different vaccine candidates will be available for A (H1N1)?

    A: About 30. Most will be inactivated virus vaccines made in eggs, some will be killed virus vaccines made in cell cultures and a few will be live attenuated virus vaccines. Then you have a lot of variation in the way vaccine is purified and in whether or not it is mixed with an additive, called an adjuvant, which is a booster of immunogenicity (which is the capacity of a vaccine to evoke an immune response) and which is used with killed virus vaccine. All vaccines create antibodies to fight the virus; some will produce a local response, such as attenuated vaccine administered in the nose to give more immunity at the port of entry of the virus. The industry will use tiered pricing, so high-income countries might pay between US$ 10–20 per dose, middle-income countries may pay about half that and low-income half that price again.



    These are ballpark figures but this is the order of magnitude.


    Q: Isn’t it too early to produce vaccines because the pandemic virus could mutate?

    A: Although the virus can mutate, we hope that there will be enough cross-protection through recognition of the new virus. But if the virus changes too much, we will need new vaccines.


    Q: WHO has recommended the use of adjuvant in pandemic vaccines, but some countries don’t plan to follow this guidance.

    A: Many countries, including the USA, have not licensed vaccines with adjuvants of any kind yet. Other vaccines with the same type of adjuvant as planned for pandemic influenza A (H1N1) vaccines have, however, been licensed in European countries. Countries that intend to use vaccine with adjuvant will find that there is a large body of safety data for adults and some for children. In any case, all countries will need to carry out good post-marketing surveillance to make sure that they pick up any early sign of a safety problem with a particular vaccine.


    Q: These must be the fastest vaccines ever produced. Given their fast-tracking, what is the guarantee of safety and efficacy?

    A: The testing of influenza vaccines is different from that of other vaccines, because the rabies and measles vaccines for example do not change. Since influenza viruses evolve constantly, it is impossible to carry out a complete clinical analysis of seasonal influenza vaccines yearly because the composition changes each year to adapt to the virus and so you are always a year behind. A complete clinical evaluation is not needed also because manufacturers produce seasonal influenza vaccines using the same procedure and equipment, but for a different virus each year. In the USA, vaccines for seasonal influenza are licensed without clinical trials on the basis of a “strain change”.



    The US regulatory authorities consider the change from seasonal to pandemic H1N1 influenza vaccine production (using the same procedure) as a change in the strain and therefore will not request clinical trials before registration. Having said that, all manufacturers will perform clinical trials to find out whether one or two doses are necessary, to test it in special populations and to administer it jointly with other vaccines. In Europe, a strain change is accompanied by a small clinical trial requested by the European Medicines Agency.



    In the last couple of years, manufacturers in the European Union registered “mock-up” or prototype H5N1 bird flu vaccines as nobody knows which H5N1 strain might become a pandemic strain. Manufacturers made clinical batches of an H5N1 vaccine with virus stocks from China, Indonesia and Viet Nam. They carried out clinical trials and submitted the results to the regulatory authorities who said the vaccines were fine. They are not allowed to sell H5N1 vaccines, since there is no H5N1 pandemic, but they can use the same procedure to make H1N1 pandemic vaccine. That way they can get a licence in a few days. This is another way vaccines can be licensed without clinical trials, while still ensuring safety on the basis of what is known about influenza vaccines.



    Based on the extensive knowledge available on seasonal vaccines and the results obtained through evaluation of H5N1 avian influenza vaccines, there is no doubt that it will be possible to make effective H1N1 pandemic vaccines.


    Q: What’s been done to ensure that developing countries get enough vaccine?

    A: It depends on what we mean by “enough”. Some countries want to vaccinate every member of the population, but there is no way we can do this for the whole world. WHO has a cross-organizational operation that is in place to secure vaccines for developing countries. This is spearheaded by the Director-General’s Office and the legal and vaccine departments. We are engaged in three types of activities.



    The first is to negotiate donations with manufacturers. Two have been announced: 100 million doses by sanofi-aventis and 50 million doses from GlaxoSmithKline. Second, we are working with other manufacturers to reserve a portion of their vaccine production for WHO at a reduced price. Third, we are working with governments to raise funds to purchase vaccines. We are also working with 11 vaccine manufacturers based in developing countries, providing them with seed financing and technical expertise to help them produce influenza vaccine domestically. We have also helped them access technology and given them sub-licences to use technology for producing live attenuated vaccine. These 11 companies will be manufacturing some of the 30 different expected vaccines.


    Q: What happens if developing countries have only partial coverage?

    A: Coverage will be partial and not only in developing countries. But we should not be “hypnotized” by vaccines. There are other measures, such as social distancing, school closure, avoidance of large gatherings, antibiotics and personal hygiene. This is not like rabies, which is 100% fatal: we are talking about a disease from which most people recover very well.



    We will try to help countries to gain access to as much vaccine as possible, at least to preserve their health systems functioning, but there is just not enough vaccine for every country in the world to vaccinate every member of the population twice. ■


    http://www.who.int/bulletin/volumes/.../en/index.html

    Leave a comment:


  • mixin
    replied
    Re: Swine flu vaccines, adjuvants, equity, safety

    Glaxo has a cervical cancer vax, Cervarix, that is anticipated to be approved by the FDA in a week or two. It contains AS04 so this will help alieviate safety concerns over the adjuvant and pave the way for its approval in other drugs according to Financial Times.

    Cervarix is approved in nearly 100 countries and has been tested here on over 18,000 women.
    --------------------------------------------

    US regulators have downplayed safety concerns over GlaxoSmithKline’s vaccine against cervical cancer in a decision that will have repercussions for many other vaccines, including those to protect against the pandemic flu virus.

    Documents made public ahead of an advisory committee of the Food & Drug Administration on Wednesday downplay previous concerns over Cervarix, paving the way for the likely approval of the first vaccine in the US in 80 years to contain a patented “adjuvant” to enhance efficacy.

    http://www.ft.com/cms/s/0/dd7c9258-9...44feabdc0.html

    Leave a comment:


  • sharon sanders
    replied
    Re: Swine flu vaccines, adjuvants, equity, safety

    Thank you everyone. Please voice your opinions. This is not a news thread. I expect a vigorous debate about the novel H1N1 09 vaccine.

    For the record - FluTrackers is 100&#37; against forced vaccination.

    We think that being vaccinated is a personal decision.

    We advocate school closures, N95 masks for health care workers, and 90 days of essential supplies per living unit.

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  • prepdeb
    replied
    Re: Swine flu vaccines, adjuvants, equity, safety

    My comments are just that - my opinions and thoughts on the subject.

    As someone with underlying health conditions who falls into one of the groups being given priority (under 64 with health problems), I haven't made a firm decision yet, but I doubt that I will have the H1N1 vaccination.

    I'm in that priority group because I was harmed by a seasonal vax in 2006. I doubt that there was anything wrong with the vaccine as supplied by the manufacturers, but it was probably not handled properly somewhere on it's path. 2006 was the only time we chose to take advantage of free drive-thru flu shots provided by our local health department and it's the only time in many years of being vaccinated, that either of us has had an adverse reaction. We both became ill within hours of receiving the jab and I developed pneumonia. The damage continued because of an incompetent physician who first provided an antibiotic that was not supposed to be used, but he hadn't read the alert. Then when my condition was worsened by the antibiotic, he refused to prescribe a different one or run any definitive tests to identify the type of pneumonia.

    Compost happens and we know going into this thing that everyone involved in the creation, production and distribution of the vaccine is provided immunity in the event problems develop.

    I'm a bit gun shy after my bad experience with a seasonal vax and a bad doctor.
    I still get seasonal flu jabs, but only use the visiting nurse service or get the shot in my doctors office (different doc, of course).

    On top of my concern over the true safety of the vaccine, whether or not it contains adjuvants, I'm not entirely sure how much protection it would provide.
    My husband and I have both been sick multiple times this summer and know many others who seem to be experiencing the same thing.
    While none of us has been tested or confirmed to have H1N1, given the symptoms, it's the most likely scenario.
    If we continue to contract it, over and over again, after having had it - how much more protection would an iffy vaccine provide?

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  • Snowy Owl
    replied
    Re: Swine flu vaccines, adjuvants, equity, safety

    I Have to Land Here,

    I read Reveres post this morning, honestly I believe any honest person could not bluntly say that we can Trust the producers of vaccines, they have cheated over and over on clinical datas, they have made (presumably made mistakes that could have killed billions Baxter) and we all know that all these are just the tip of the Iceberg.

    What will happened is that vulnerable people will be the guinea pigs, in rich and poor countries.

    Some in desesperation might opt for the vaccine and I understand that and probably in the majority of cases it should be fine.

    But for all of those who knows how to avert or treat an infection and taking into considerations their environment (arsenic, nitrites, etc..) the climate, the social mood and their access to alternatives options should back off and wait until spring if possible.

    But it is an individual choice, but people should be aware of what big pharma have done at the expenses of poor people and the absence of ethics guiding those entreprises.

    Finally not being allowed to sue big pharma looks like govs have been blackmail either we have a waiver or you're gonna wait.

    To be coherent vaccination should be consider as an essential service and should be control and produced by the government not by the second most paying multinational in the world after the arms dealers of course.

    Snowy Owl

    Gov get into nuclear reactors to check if everything is ok why dont they do the same thing with big pharma?

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