Vaccine found against Bird Flu

[FluBossie]

Vaccine found against bird flu
From our reporter Broer Scholtens
published on 03 January 2008 02.51, updated on 3 January 2008 10.13

AMSTERDAM - the British pharmaceutical company GSK has developed a vaccine against the notorious H5N1-bird flu virus. This virus has killed the past three years millions of birds, especially in Asian countries. Approximately 350 people have been infected, the most in Vietnam and Indonesia; two third died directly after contraction of the virus.

The vaccine offers protection against several worldwide spread influenza virus-strains: not only against H5N1-bird flu virus, of which samples have been taken from deceased in Vietnam, but also against a related virus strain which has been found in Indonesia.

Ferrets
This becomes clear from a study of ViroClinics, a little company at the Erasmus Medical Centre in Rotterdam, which tested the vaccine on about twenty ferrets. The airways of ferrets resemble much those of people. The research results have been put today on the scientific site PloSone.

H5N1-virus constantly changes conformation: it adapts to people. As a result, the risk that people infect each other becomes larger. The World Health Organisation (WHO) predicts the development of a pandemic strain of this virus which will infect people on a large scale. An estimated 20 per cent of the world population will become sick. The WHO assumes millions deads worldwide.

Pandemic strain.
A protective vaccine can be made only just after a first large outbreak: then the exact conformation of pandemic strain has been determined. Then it lasts still six months before a vaccine on large scale is available.

Vaccine company GSK reaches broader protection by addition of an adjuvant, a substance which reinforces the response of the immune system. The idea is that as a result, a pandemic vaccine can be made and stored already. When the pandemic strain emerges people can be directly vaccinated.

http://www.volkskrant.nl/binnenland/article491570.ece/Vaccin_gevonden_tegen_vogelgriep

[FluBossie]

Re: Vaccine found against Bird Flu

Here the article in PlosOne.

[FluBossie]

Re: Vaccine found against Bird Flu

Breakthrough in effective bird flu vaccine
by Willemien Groot*

03-01-2008

There has been a new step forward in the development of an effective vaccine against H5N1, the bird flu virus that's also dangerous to humans. By adding an agent that stimulates the immune system, it appears that the existing vaccine is effective against various strains of the bird flu virus.

Uncertainty has been the biggest problem in developing an effective vaccine against the variant of H5N1 that's dangerous to humans. Uncertainty about which strain of the virus it is, and uncertainty over which type of bird flu could develop into a flu virus that might cause a worldwide epidemic. That made it almost impossible to develop a preventative vaccine. But with the discovery made by the British pharmaceutical company Glaxo Smith Klein, uncertainty over the virus strain has become less significant.

Breakthrough
The improved vaccine has been tested by Viro-Clinics, part of the Erasmus Medical Centre in Rotterdam. According to virologist Ab Osterhaus, there are several reasons to speak of a breakthrough:

"The vaccine protects against different variants of the H5N1 virus, including new strains."

According to the virologist, that's unique.

"We have always had to react after the event, but now we can produce a vaccine that offers protection against new and forthcoming variants of the same virus."

What's more, tests have shown that by adding the agent, a lot less vaccine is required. And that's very important during a worldwide flu epidemic, when huge quantities of vaccine are needed.

Response
The agent is a so-called adjuvant that is added to a medicine to strengthen its effectiveness. In this case, the substance stimulates the immune system and improves the response to the vaccine. The Erasmus Medical Centre tested the agent on people and on ferrets which, like people, suffer from flu viruses. Osterhaus explained the results:

"The humans appeared to have a relatively broad immune response. The ferrets were first vaccinated, then exposed to H5N1, and there too we witnessed a demonstrably broad protection against the virus."

Pandemic
H5N1 is generally regarded as the bird flu virus that can develop into a pandemic virus. It first appeared in Asia in 1996, and then spread very quickly across the whole world. In Africa, Europe and the Middle East the virus was subsequently identified. Millions of poultry were killed, and more than a hundred people died as a result of the flu virus.

H5N1 is one of the high-pathogenic viruses: 90 percent of people who are affected eventually die. Up to now, the virus has not mutated into a variant that can be passed from one human to another.

The World Health Organisation (WHO) regards the virus as the major potential cause of a pandemic, but there are other types. Spanish flu, which killed 50 million people worldwide in 1918, was of the type H1N1.

Supplies
Osterhaus is pleading for the supply of large quantities of the vaccine and adjuvant against H5N1. As soon as the flu virus develops into a variant which can be passed on from person to person, and a pandemic is lurking, the adjuvant can be added to the vaccine. In addition, supplies of antiviral agents such as Tamiflu must remain at the same level.

Although it is not certain that H5N1 will develop into a pandemic virus, virologist Ab Osterhaus pleads for vigilance:

"The danger to humans will always remain. With this discovery it's possible to prevent many infections at an early stage. But if the virus is of a different subtype, the production of a new vaccine will take at least several months."

http://www.radionetherlands.nl/currentaffairs/080103-bird-flu-vaccine

[Shannon Bennett]

Re: Vaccine found against Bird Flu

The study included healthy adults 18-60 years of age.

They reported the vaccine was well-tolerated in all subjects.

I haven't seen if any dropped out of the study for whatever reason.

They tested the adjuvant the new vaccine on 24 ferrets. They vaccinated the ferrets twice, on day 0 and day 21. Within this study there were three groups one using the adjuvant in the vax and one without and one the adjuvant by itself. On day 49 they infected them with a lethal dose of A/Indonesia/5/2005.

All of the ferrets either died or were moribund that did not receive the adjuvanated vaccine. Of the ferrets receiving the vaccine plus adjuvant all but one survived and it was given the smallest amount of adjuvant. Very high viral loading was found in those not receiving the adjuvanated vax (av). Much lower viral loading was found in the av group.

The av group also showed far less viral shedding as compared to the other two groups.

They did say the adjuvant was an oil and water based one but did not share with us what it actually was. Since there have been problems in the past with some oil & water adjuvants, many of them serious, I would like to examine the results of the adjuvant testing on humans.

I would also like to know how long it would take to make the adjuvant and how much it costs. I would also very much like to see this vax tested on other populations.

[tropical]

Re: Vaccine found against Bird Flu

"FW": "Universal Influenza Vaccine"

http://www.businesswire.com/portal/site/topix/index.jsp?ndmViewId=news_view&newsId=20080103005371&newsLang=en&ndmConfigId=1000639&vnsId=41

ACAMBIS
January 03, 2008 04:11 AM Eastern Time

Positive Phase I and Pre-Clinical Data Suggest Acambis?

M2e-Based Universal Influenza Vaccine, ACAM-FLU-A?, Could Tackle Influenza Pandemics

CAMBRIDGE, England and CAMBRIDGE, Mass.--(BUSINESS WIRE)--Acambis plc (Acambis) (LSE:ACM), a leading vaccine development company, today announced positive data from two trials of its universal influenza vaccine ACAM-FLU-A?. The novel vaccine targets the M2e peptide, which is found unchanged on the surface of all ?A? strains of the influenza virus, including all pandemic influenza strains. As such, this vaccine could overcome the current need to adapt influenza vaccines every year to correspond to circulating strains. The Phase 1 clinical trial showed the vaccine to be well tolerated and immunogenic and the pre-clinical challenge study suggests that this M2e-based vaccine can protect against highly pathogenic viruses such as pandemic influenza strains, including H5N1.
Currently, influenza vaccines are regularly reformulated owing to the rapid mutation of the virus. ACAM-FLU-A? combines the conserved M2e peptide with a carrier molecule from Hepatitis B, which is used to help stimulate the immune system. This novel vaccine design means that ACAM-FLU-A? could potentially provide protection against ?A? strains of influenza. Historically, influenza pandemics have only been caused by ?A? strains of the virus. Therefore ACAM-FLU-A? has potential both as a vaccine against pandemic influenza and as part of seasonal influenza vaccination.
The Phase 1 trial was a double-blind, placebo-controlled study conducted at three centres in the USA. The study consisted of four arms: placebo, ACAM-FLU-A? alone or combined with aluminium hydroxide or QS-21. Healthy volunteers aged between 18 and 40 were given two doses 30 days apart, their immune response against the M2 protein was tested after 60 days and any adverse events to the vaccine were recorded.
The vaccine was shown to be immunogenic and well-tolerated, with no serious adverse events. Whilst immune responses were seen in all the vaccinated groups, blood tests showed that the highest immune responses occurred in the group who received ACAM-FLU-A? with QS-21. In this group, 90% of people who received ACAM-FLU-A? plus QS-21 had antibodies to the M2 protein in their system. QS-21 Stimulon? adjuvant is an investigational adjuvant (immune stimulant) provided under an agreement with Antigenics Inc., which has recently been converted to a non-exclusive license and supply agreement.
The pre-clinical study tested the ability of an M2e-based vaccine to protect against the Vietnam 2004 strain(1) of H5N1 avian influenza (bird flu). The H5N1 virus was lethal in the placebo-treated group, whereas 70% of those in the group vaccinated with the M2e-based vaccine from the same influenza strain were protected.
Dr Michael Watson, Executive Vice President, Research & Development at Acambis commented: ?Taken together, the data from these two trials demonstrate the potential of Acambis? approach to offer protection against ?A? strains of the influenza virus, including pandemic influenza strains. As a universal vaccine, ACAM-FLU-A? can potentially overcome many of the drawbacks of existing influenza vaccines. It can be manufactured at any time of the year, and could be stockpiled in advance of a pandemic or potentially used routinely to ensure population protection against future pandemics.?
Following these results, Acambis will explore partnering in parallel with continued development of ACAM-FLU-A?.
About Acambis
Acambis is a leading vaccine company developing novel vaccines that address significant unmet medical needs or substantially improve standards of care. ChimeriVax?-JE, Acambis? most advanced product in its development-stage pipeline, has to date shown an excellent safety and efficacy profile following pivotal Phase 3 trials. It is currently undergoing paediatric trials in India and is partnered with Sanofi Pasteur and Bharat Biotech. Acambis? proprietary ChimeriVax? technology, developed in association with St Louis University, has also been used to develop ChimeriVax?-West Nile, which is undergoing Phase 2 clinical testing, making it the most advanced investigational vaccine against the West Nile virus. Acambis has established a global collaboration with Sanofi Pasteur for further development and commercialisation of the vaccine. ChimeriVax? has also been applied to development of Sanofi Pasteur?s tetravalent dengue vaccine, which has successfully demonstrated proof-of-concept in a Phase 2 trial by generating 100% seroconversion to all four dengue virus serotypes.
Acambis also has the only vaccine in development against Clostridium difficile bacteria, a leading cause of hospital-acquired infections. C. difficile is estimated to cause at least 360,000 cases of C. difficile-associated disease in the US alone with annual costs to the healthcare system of $3.2bn. Acambis? influenza programme aims to develop a universal vaccine against influenza, for which a universal ?A? strain vaccine, ACAM-FLU-A?, has completed a Phase 1 trial. It also includes various further vaccine candidates in the research and pre-clinical stages.
Acambis is recognised internationally as the leading producer of smallpox vaccines. Acambis? ACAM2000? (Smallpox (Vaccinia) Vaccine, Live) vaccine for active immunisation against smallpox disease for persons determined to be at high risk for smallpox infection was licensed by the US Food and Drug Administration in August 2007. Acambis has manufactured doses of ACAM2000? for emergency-use stockpiles held by the US Government and several other governments around the world. For safety and prescribing information, please refer to www.acambis.com/ACAM2000.
Acambis is based in Cambridge, UK and Cambridge, Massachusetts, US, and is listed on the London Stock Exchange (ACM). More information is available at www.acambis.com.
About influenza and influenza vaccines
Today, seasonal influenza represents the single largest vaccine market in the world, worth an estimated $2.2bn and projected to grow to $4bn by 2010(3). It is still a major global threat, which the WHO estimates causes between 250,000 and 500,000 deaths every year around the world(2)..Immunity against influenza viruses, whether acquired by natural infection or immunisation, is typically transient due to the virus?s ability to mutate and evade pre-existing immunity. Accordingly, current licensed vaccines are updated on an annual basis to target most effectively the presently circulating strains.
Pandemic influenza viruses are sufficiently distinct from seasonal epidemic viruses that new vaccines must be developed to address them. Pandemic influenza vaccines, primarily targeting avian H5N1 viruses, are being stockpiled for emergency use. However, the efficacy of these vaccines may be negatively impacted by continual mutations in circulating H5N1 strains. Experts believe the next pandemic could cause disease in two billion people. Based on best-case scenarios modelled on the mild pandemic of 1968, this could result in two to seven million deaths. However, if the death toll associated with the 1918 influenza virus were applied to today?s world population, there could be 180 to 360 million deaths globally.(4)
Currently, influenza vaccines are reformulated, generally each year, to address mutations in influenza strains (known as ?antigenic drift?). Preparations are ongoing around the world for a potential pandemic, which would result from a major genetic change in the influenza virus (known as ?antigenic shift?). The need to change vaccine formulations each year results in delays in initiating vaccination programmes. In addition, it is estimated that vaccine producers would need between three and six months to product a strain-specific vaccine against a pandemic strain.
About ACAM-FLU-A?
ACAM-FLU-A? is a recombinant vaccine that uses a hepatitis B core protein (HBc) to present M2e, the extracellular domain of the ion channel protein M2(5). M2 is one of the three proteins expressed on the surface of the ?A? strain influenza virus and of infected cells alongside haemagglutinin (HA) and neuraminidase (NA). Unlike HA and NA, M2 is highly conserved, albeit under natural conditions not easily recognised by the immune system. M2e could elicit an immune response to all influenza ?A? strains. As such, ACAM-FLU-A? has the potential to be both a universal pandemic or pre-pandemic influenza vaccine and part of a universal seasonal vaccine. Historically, influenza pandemics have been caused by ?A? strains of the virus while seasonal vaccines target both ?A? and ?B? strains of the virus.
References
(1) The Vietnam 2004 Clade 1 avian influenza virus has been used by manufacturers to develop and produce pre-pandemic vaccines. http://www.who.int/csr/disease/avian_influenza/guidelines/recommendati onvaccine.pdf
(Due to its length, this URL may need to be copied/pasted into your Internet browser's address field. Remove the extra space if one exists)
(2) WHO: http://www.who.int/mediacentre/factsheets/fs211/en/
(3) Datamonitor
(4) Kamps-Hoffmann-Preiser, Influenza Report 2006
(5) Neirynck et al., Nature Medicine, 5, 1157, 1999
?Safe Harbour? statement
Statements contained within this news release may contain forward-looking comments, which involve risks and uncertainties that may cause actual results to vary from those contained in the forward-looking statements. In some cases, you can identify such forward-looking statements by terminology such as 'may', 'will', 'could', 'forecasts', 'expects', 'plans', 'anticipates', 'believes', 'estimates', 'predicts', 'potential', or 'continue'. Predictions and forward-looking references in this news release are subject to the satisfactory progress of research which is, by its very nature, unpredictable. Forward projections reflect management's best estimates based on information available at the time of issue.
Contacts
Acambis plc
Ian Garland, Chief Executive Officer
Dr Michael Watson, Executive VP, R&D
Lyndsay Wright, VP, Communications and IR
Tel: +44 (0) 1223 275 300
or
College Hill
Lorna Cuddon, Katie Odgaard, Gemma Price
Tel: +44 (0)20 7457 2020
acambis@collegehill.com

[Shannon Bennett]

Re: Vaccine found against Bird Flu

I am glad there are people in the world dedicated to making vaccines targeting H5N1. Having said that, I would like to remind everyone now is the time to be a critical thinker, in not only the efficacy but, the safety of vaccines. We need to examine carefully not the hype but the methods, the manufacturers, the doctors-both their reputations as well as their accomplishments and education, and the track record of the company. How many were tested? Which populations were tested and what were the results. Saying the vaccine was well-tolerated isn't enough. We need to see exactly what happened in the trials. Did any drop out for any reason? What does no serious adverse effects actually mean? Which adjuvant are they using? These and other questions are what we should be looking for now when we have the time to make sure we aren't exchanging one disaster for another.

[gsgs]

Re: Vaccine found against Bird Flu

maybe this wasn't reported so much in USA because it's a non-American
vaccine ?
Much more coverage about the Fauci,Webster,Sanofi vaccines
in the last years which didn't go so well.

Is this really all about getting the best vaccine coverage
or is a national race who comes first up with a vaccine for
good prices ?
The $7B in 2005, the plant in Holly Springs, the fixation on Sanofi,
was it really the best choice, was it necessary ?
USA could as well buy vaccine from Europe through APAs.
It could still be economically reasonable, what they did.
But don't tell the people: "else there would be no vaccine".
Tell them : "else the vaccine would be more expensive"

[Shannon Bennett]

Re: Vaccine found against Bird Flu

It would be troubling if this company used Squalene and detergent as the adjuvant. The link is to Fluwiki2 with a hat-tip to anon.yyz at curevents.

http://newfluwiki2.com/showComment.do;jsessionid=E20A300D29B12AC98AABD6005F82A3E9?commentId=79502

also see here.

http://newfluwiki2.com/showDiary.do?diaryId=1772

[Shannon Bennett]

Re: Vaccine found against Bird Flu

GSGS, found in a link at Fluwiki, this is an easy to understand article on how companies, governments, etc,... get around actually telling us what we need to know. I think you will get a kick out of the article. VERY interesting and, after reading it I know my own critical reading skills have improved.

http://scienceblogs.com/denialism/deck.php