Giuseppe
Emeritus
[In this post: (1) Research Articles Abstracts.
Contents:
(1.1) Prospective evaluation of rapid antigen tests for diagnosis of respiratory syncytial virus and human metapneumovirus infections.
(1.2) Identifying infections with respiratory syncytial virus by using specific immunoglobulin G (IgG) and IgA enzyme-linked immunosorbent assays with oral-fluid samples.
(1.3) Anti-Ganglioside Antibody Induction by Swine (A/NJ/1976/H1N1) and Other Influenza Vaccines: Insights into Vaccine-Associated Guillain-Barr? Syndrome.
(1.4) Prevention of Symptomatic Seasonal Influenza in 2005-2006 by Inactivated and Live Attenuated Vaccines.
(1.5) Plasmid DNA-Based Vaccines Protect Mice and Ferrets against Lethal Challenge with A/Vietnam/1203/04 (H5N1) Influenza Virus
(1.6) Influenza virus infection augments NK cell inhibition through the reorganization of MHC class I proteins.
(1.7) The role of interferon in the replication of human parainfluenza virus type 1 wild type and mutant viruses in human ciliated airway epithelium.
(1.8) Acute lower respiratory tract infection.
(1.9) Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus.
(1.10) High titer growth of human and avian influenza viruses in an immortalized chick embryo cell line without the need for exogenous proteases.
(1.11) The effectiveness of national influenza vaccination policies for at-risk populations over 5 seasons in a Scottish general practice.
(1.12) Optimal allocation of pandemic influenza vaccine depends on age, risk and timing.
(1.13) Antibody and T-cell responses to a virosomal adjuvanted H9N2 avian influenza vaccine: Impact of distinct additional adjuvants.
(1.14) Report of the 4th meeting on the "Evaluation of pandemic influenza prototype vaccines in clinical trials"
(1.15) Development of a universal influenza A vaccine based on the M2e peptide fused to the papaya mosaic virus (PapMV) vaccine platform.
(1.16) Nasal continuous positive airway pressure with heliox versus air oxygen in infants with acute bronchiolitis: a crossover study.
See original abstracts at the source site. EDITED.]
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(1.1): J Clin Microbiol. 2008 May;46(5):1682-5. Epub 2008 Mar 12.
Prospective evaluation of rapid antigen tests for diagnosis of respiratory syncytial virus and human metapneumovirus infections.
Aslanzadeh J, Zheng X, Li H, Tetreault J, Ratkiewicz I, Meng S, Hamilton P, Tang YW. - Hartford Hospital and Clinical Laboratory Partners, Hartford, Connecticut 06102, USA. Jaslanz@harthosp.org
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two important viral pathogens that cause respiratory tract infections in the pediatric population.
The rapid detection of these agents allows the prompt isolation and treatment of infected patients.
In the present prospective study, we evaluated the performances of four rapid antigen detection assays, including a rapid chromatographic immunoassay (CIA) for RSV (Directigen EZ RSV; Becton Dickinson, Sparks, MD), a direct fluorescent-antibody assay (DFA) for RSV (Bartels; Trinity Biotech, Carlsbad, CA), and two DFAs for hMPV manufactured by Diagnostic Hybrids Inc. (DHI; Athens, OH) and Imagen (Oxoid Ltd., Basingstoke, Hampshire, United Kingdom).
The clinical specimens tested comprised 515 nasopharyngeal aspirates submitted to the Clinical Microbiology Laboratory at Hartford Hospital from 1 November 2006 to 21 April 2007.
Compared to the results of real-time reverse transcription-PCR (RT-PCR), the CIA had a sensitivity of 79.8% and a specificity of 89.5%.
The RSV DFA with Bartels reagents showed a sensitivity of 94.1% and a specificity of 96.8%.
For hMPV, the sensitivity and specificity were 62.5% and 99.8%, respectively, for the DHI DFA and 63.2% and 100%, respectively, for the Imagen DFA.
The hands-on and test turnaround times for CIA were 10 and 30 to 60 min, respectively, and the hands-on and test turnaround times for the RSV and hMPV DFAs were 30 and 105 min, respectively.
We conclude that while the RSV CIA is user-friendly, it lacks sensitivity and specificity, especially during off-peak months. In contrast, the RSV DFA is more sensitive and specific, but interpretation of its results is subjective and it demands technical time and expertise.
Similarly, both hMPV DFAs are highly specific in comparison to the results of RT-PCR, but their sensitivities await further improvements.
PMID: 18337386 [PubMed - indexed for MEDLINE] - PMCID: PMC2395112 [Available on 09/01/08]
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(1.2): J Clin Microbiol. 2008 May;46(5):1659-62. Epub 2008 Feb 27.
Identifying infections with respiratory syncytial virus by using specific immunoglobulin G (IgG) and IgA enzyme-linked immunosorbent assays with oral-fluid samples.
Okiro EA, Sande C, Mutunga M, Medley GF, Cane PA, Nokes DJ. - Centre for Geographic Medicine Research--Coast, Kenya Medical Research Institute/Wellcome Trust Research Programme, Kilifi, Kenya. eokiro@nairobi.kemri-wellcome.org
Currently, respiratory syncytial virus (RSV) infection is identified in epidemiological studies by virus antigen or nucleic acid detection in combination with serology.
Oral-fluid specimens may provide a noninvasive alternative to blood, and oral fluid is more suitable for sampling outside of the clinic setting.
We evaluated an indirect enzyme-linked immunosorbent assay for the detection of RSV-specific immunoglobulin G (IgG) and IgA by using oral-fluid samples collected from individuals with RSV infections confirmed by an immunofluorescent antibody test.
For five children sampled repeatedly from birth, antibody profiles in oral fluid quite consistently tracked those in paired sera, and RSV infections were detected by rising titers of antibodies of at least one Ig class.
Specific IgG responses were generally more reliable than IgA responses, except in early infancy, where the reverse was sometimes true.
For a further five young children from whom oral fluid was collected weekly following RSV infection, boosted antibody responses, frequently of a transient nature, lasting a few weeks, were observed; specific IgG responses were of longer duration and more pronounced than specific IgA responses.
Our data show significant promise for the use of oral fluid alone in RSV infection surveillance.
The observed rapid dynamics of the antibody responses are informative in defining study sampling intervals.
PMID: 18305129 [PubMed - indexed for MEDLINE] - PMCID: PMC2395083 [Available on 09/01/08]
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(1.3): J Infect Dis. 2008 Jun 3. [Epub ahead of print]
Anti-Ganglioside Antibody Induction by Swine (A/NJ/1976/H1N1) and Other Influenza Vaccines: Insights into Vaccine-Associated Guillain-Barr? Syndrome.
Nachamkin I, Shadomy SV, Moran AP, Cox N, Fitzgerald C, Ung H, Corcoran AT, Iskander JK, Schonberger LB, Chen RT. - 1Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia; 2Centers for Disease Control and Prevention, Atlanta, Georgia; 3Department of Microbiology, National University of Ireland, Galway.
Background.
Receipt of an A/NJ/1976/H1N1 "swine flu" vaccine in 1976, unlike receipt of influenza vaccines used in subsequent years, was strongly associated with the development of the neurologic disorder Guillain-Barr? syndrome (GBS). Anti-ganglioside antibodies (e.g., anti-GM(1)) are associated with the development of GBS, and we hypothesized that the swine flu vaccine contained contaminating moieties (such as Campylobacter jejuni antigens that mimic human gangliosides or other vaccine components) that elicited an anti-GM(1) antibody response in susceptible recipients.
Methods
Surviving samples of monovalent and bivalent 1976 vaccine, comprising those from 3 manufacturers and 11 lot numbers, along with several contemporary vaccines were tested for hemagglutinin (HA) activity, the presence of Campylobacter DNA, and the ability to induce anti-Campylobacter and anti-GM(1) antibodies after inoculation into C3H/HeN mice.
Results.
We found that, although C. jejuni was not detected in 1976 swine flu vaccines, these vaccines induced anti-GM(1) antibodies in mice, as did vaccines from 1991-1992 and 2004-2005. Preliminary studies suggest that the influenza HA induces anti-GM(1) antibodies.
Conclusions.
Influenza vaccines contain structures that can induce anti-GM(1) antibodies after inoculation into mice. Further research into influenza vaccine components that elicit anti-ganglioside responses and the role played by these antibodies (if any) in vaccine-associated GBS is warranted.
PMID: 18522505 [PubMed - as supplied by publisher]
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(1.4): J Infect Dis. 2008 Jun 3. [Epub ahead of print]
Prevention of Symptomatic Seasonal Influenza in 2005-2006 by Inactivated and Live Attenuated Vaccines.
Ohmit SE, Victor JC, Teich ER, Truscon RK, Rotthoff JR, Newton DW, Campbell SA, Boulton ML, Monto AS. - 1University of Michigan School of Public Health, Department of Epidemiology, 2University of Michigan Hospitals, Department of Pathology, Ann Arbor, 3Central Michigan University Health Services, Mount Pleasant, Michigan; 4Program for Appropriate Technology in Health, Seattle, Washington.
Background.
The efficacy of influenza vaccines may vary annually. In 2004-2005, when antigenically drifted viruses were circulating, a randomized, placebo-controlled trial involving healthy adults showed that inactivated vaccine appeared to be efficacious, whereas live attenuated vaccine appeared to be less so.
Methods.
In 2005-2006, we continued our trial, examining the absolute and relative efficacies of the live attenuated and inactivated vaccines in preventing laboratory-confirmed symptomatic influenza.
Results.
A total of 2058 persons were vaccinated in October and November 2005. Studywide influenza activity was prolonged but of low intensity; type A (H3N2) virus was circulating, which was antigenically similar to the vaccine strain. The absolute efficacy of the inactivated vaccine was 16% (95% confidence interval [CI], -171% to 70%) for the virus identification end point (virus isolation in cell culture or identification through polymerase chain reaction) and 54% (95% CI, 4%-77%) for the primary end point (virus isolation or increase in serum antibody titer). The absolute efficacies of the live attenuated vaccine for these end points were 8% (95% CI, -194% to 67%) and 43% (95% CI, -15% to 71%), respectively.
Conclusions.
With serologic end points included, efficacy was demonstrated for the inactivated vaccine in a year with low influenza attack rates. The efficacy of the live attenuated vaccine was slightly less than that of the inactivated vaccine, but not statistically greater than that of the placebo. Trial registration. ClinicalTrials.gov identifier: NCT00133523 .
PMID: 18522501 [PubMed - as supplied by publisher]
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(1.5): J Infect Dis. 2008 Jun 15;197(12):1643-1652.
Plasmid DNA-Based Vaccines Protect Mice and Ferrets against Lethal Challenge with A/Vietnam/1203/04 (H5N1) Influenza Virus.
Lalor PA, Webby RJ, Morrow J, Rusalov D, Kaslow DC, Rolland A, Smith LR. - 1Vical, Inc., San Diego, California; 2Division of Virology, Department of Infectious Diseases, St. Jude Children?s Research Hospital, Memphis, Tennessee.
Plasmid DNA (pDNA) vaccines represent an alternative to conventional inactivated influenza vaccines that are likely to experience supply constraints during a pandemic.
Several Vaxfectin-formulated pDNA vaccines were tested in mice and ferrets for efficacy against a lethal challenge with the highly pathogenic A/Vietnam/1203/04 (H5N1) influenza virus strain; the vaccines encoded influenza A virus hemagglutinin (HA), and/or nucleoprotein (NP), and M2 protein.
Complete protection from death and disease was achieved in mice and ferrets with 2 doses of a Vaxfectin-formulated vaccine containing H5 HA, NP, and M2 plasmids and in ferrets with only 1 dose.
A Vaxfectin-formulated vaccine containing NP and M2 pDNA provided significant protection against death in mice and provided some benefit in ferrets (i.e., 17% survival, delayed time to illness and death, and significant reduction in viral load compared with that in negative control animals).
These experiments support the clinical testing of pDNA vaccine candidates that may ultimately increase global vaccine supply options during pandemics.
PMID: 18513153 [PubMed - as supplied by publisher
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(1.6): J Virol. 2008 Jun 4. [Epub ahead of print]
Influenza virus infection augments NK cell inhibition through the reorganization of MHC class I proteins.
Achdout H, Manaster I, Mandelboim O. - The Lautenberg Center for General and Tumor Immunology, the Hebrew University Hadassah Medical School, Jerusalem, 91120, Israel.
The killing by Natural Killer (NK) cells is regulated by inhibitory, costimulatory and activating receptors.
The inhibitory receptors recognize mainly MHC class I molecules, while the activating NK receptors recognize stress induced ligands and viral products.
Thus, changes in the expression of the various inhibitory and activating ligands will determine whether target cells will be killed or protected.
Here we demonstrate that following influenza infection the binding of the two NK inhibitory receptors; KIR2DL1 and the LIR1 to the infected cells is specifically increased.
The increased binding occurs shortly after the influenza infection, prior to the increased recognition of the infected cells by the NK activating receptor, NKp46.
We also elucidate the mechanism responsible for this effect and demonstrate that following influenza virus infection, MHC class I proteins redistribute on the cell surface and accumulate in the lipid rafts microdomains.
Such redistribution allows better recognition by NK inhibitory receptors and consequently increases resistance to NK cell attack.
In contrast, T cell activity was not influenced by the redistribution of MHC class I proteins.
Thus, we present here a novel mechanism, developed by the influenza virus, of inhibition of NK cell cytotoxicity, through the reorganization of MHC class I proteins on the cell surface.
PMID: 18524833 [PubMed - as supplied by publisher]
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(1.7): J Virol. 2008 Jun 4. [Epub ahead of print]
The role of interferon in the replication of human parainfluenza virus type 1 wild type and mutant viruses in human ciliated airway epithelium.
Bartlett EJ, Hennessey M, Skiadopoulos MH, Schmidt AC, Collins PL, Murphy BR, Pickles RJ. - Laboratory of Infectious Diseases, Respiratory Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services. Bethesda, MD, 20892-2007, USA; Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill. Chapel Hill, NC, 27599-7248, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill. Chapel Hill, NC, 27599-7248, USA.
Human parainfluenza virus type 1 (HPIV1) is a significant cause of pediatric respiratory disease, in the upper and lower airways.
An in vitro model of human ciliated airway epithelium (HAE), a useful tool for studying respiratory virus-host interactions, was used in this study to show that HPIV1 selectively infects ciliated cells within the HAE and that progeny virus is released from the apical surface with little apparent gross cytopathology.
In HAE, type I interferon (IFN) is induced following infection with a HPIV1 mutant expressing defective C proteins with a F170S amino acid substitution, rHPIV1-C(F170S), but not following infection with HPIV1 wild type (wt).
IFN induction coincided with a 100 to 1000-fold reduction in virus titer, supporting the hypothesis that the HPIV1 C proteins are critical for inhibition of the innate immune response.
Two recently characterized live attenuated HPIV1 vaccine candidates expressing mutant C proteins were also evaluated in HAE.
The vaccine candidates, rHPIV1-C(R84G/Delta170)HN(T553A)L(Y942A) and rHPIV1-C(R84G/Delta170)HN(T553A)L(Delta1710-11), which contain temperature sensitive (ts) attenuating (att) and non-ts att mutations, were highly restricted in growth in HAE at permissive (32 degrees C) and restrictive (37 degrees C) temperatures.
The viruses grew slightly better at 37 degrees C than at 32 degrees C, and rHPIV1-C(R84G/Delta170)HN(T553A)L(Y942A) was less attenuated than rHPIV1-C(R84G/Delta170)HN(T553A)L(Delta1710-11).
The level of replication in HAE correlated with that previously observed in African green monkeys, suggesting that the HAE model has potential as a tool for pre-clinical evaluation of HPIV1 vaccines, although how these in vitro data will correlate with vaccine virus replication in seronegative human subjects remains to be seen.
PMID: 18524813 [PubMed - as supplied by publisher]
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(1.8): N Engl J Med. 2008 May 29;358(22):2413-4; author reply 2414.
Comment on: N Engl J Med. 2008 Feb 14;358(7):716-27.
Acute lower respiratory tract infection.
Eisenhut M.
PMID: 18509133 [PubMed - indexed for MEDLINE]
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(1.9): Proc Natl Acad Sci U S A. 2008 Jun 3. [Epub ahead of print]
Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus.
Zheng BJ, Chan KW, Lin YP, Zhao GY, Chan C, Zhang HJ, Chen HL, Wong SS, Lau SK, Woo PC, Chan KH, Jin DY, Yuen KY. - State Key Laboratory of Emerging Infectious Diseases.
The mortality of human infection by influenza A/H5N1 virus can exceed 80%.
The high mortality and its poor response to the neuraminidase inhibitor oseltamivir have been attributed to uncontrolled virus-induced cytokine storm.
We challenged BALB/c mice with 1,000 LD(50) of influenza A/Vietnam/1194/04.
Survival, body weight, histopathology, inflammatory markers, viral loads, T lymphocyte counts, and neutralizing antibody response were documented in infected mice treated individually or in combination with zanamvir, celecoxib, gemfibrozil, and mesalazine.
To imitate the real-life scenario, treatment was initiated at 48 h after viral challenge.
There were significant improvements in survival rate (P = 0.02), survival time (P < 0.02), and inflammatory markers (P < 0.01) in the group treated with a triple combination of zanamivir, celecoxib, and mesalazine when compared with zanamivir alone.
Zanamivir with or without immunomodulators reduced viral load to a similar extent.
Insignificant prolongation of survival was observed when individual agents were used alone.
Significantly higher levels of CD4(+) and CD8(+) T lymphocytes and less pulmonary inflammation were also found in the group receiving triple therapy.
Zanamivir alone reduced viral load but not inflammation and mortality.
The survival benefits of adding celecoxib and mesalazine to zanamivir could be caused by their synergistic effects in reducing cytokine dysfunction and preventing apoptosis.
Combinations of a neuraminidase inhibitor with these immunomodulators should be considered in randomized controlled treatment trials of patients suffering from H5N1 infection.
PMID: 18523003 [PubMed - as supplied by publisher
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(1.10): Vaccine. 2008 May 8. [Epub ahead of print]
High titer growth of human and avian influenza viruses in an immortalized chick embryo cell line without the need for exogenous proteases.
Smith KA, Colvin CJ, Weber PS, Spatz SJ, Coussens PM. - Molecular Pathogenesis Laboratory, Department of Animal Science, Michigan State, University, East Lansing, Michigan, USA.
The current method of growing influenza virus for vaccine production is through the use of embryonated chicken eggs.
This manufacturing system yields a low concentration of virus per egg, requires significant downstream production for purification, and demands a considerable amount of time for production.
We have demonstrated an immortalized chick embryo cell line, termed PBS-1, is capable of growing unmodified recent isolates of human and avian influenza A and B viruses to extremely high titers.
In many cases, PBS-1 cells out perform primary chick embryo kidney (CEK) cells, Madin-Darby Canine Kidney (MDCK) cells and African green monkey kidney cells (Vero) in growth of recent influenza isolates.
PBS-1 cells are free of any exogenous agents, are non-tumorigenic, and are readily adaptable to a variety of culture conditions, including growth on microcarrier beads.
Influenza viruses grown in PBS-1 cells are released into the culture fluid without the need for exogenous proteases, thus simplifying downstream processing.
In addition to offering a significant improvement in vaccine production, PBS-1 cells should prove valuable in diagnostics and as a cell line of choice for influenza virus research.
PMID: 18524432 [PubMed - as supplied by publisher]
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(1.11): Vaccine. 2008 May 5. [Epub ahead of print]
The effectiveness of national influenza vaccination policies for at-risk populations over 5 seasons in a Scottish general practice.
Sivaprakasam V, Douglas J, Selvaraj S, Macintyre S, Carman WF. - West of Scotland Specialist Virology Centre, Glasgow, Scotland, UK.
AIM:
To determine the effectiveness of serial influenza vaccination.
SCOPE:
Studied in a Scottish GP population, the overall seroresponse rate increased with annual influenza vaccinations and after 5 years it increased from 45.1% to 93.3% for influenza virus A (H1) and from 48.4% to 98.3% for influenza virus A (H3). However, there was little boosting effect with further doses after becoming a seroresponder. The pre-vaccination titres were significantly higher in previous year's seroresponders compared to non-responders.
CONCLUSIONS:
The policy of annual vaccination is supported by our data in order to increase the disappointing response rate after one dose. However, the lack of a boosting response with subsequent doses and the significant residual immunity after becoming a seroresponder suggests a prior serological immunity check in order to better direct the vaccine supply (in the years of no antigenic drift), to those who need it most.
PMID: 18524431 [PubMed - as supplied by publisher]
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(1.12): Vaccine. 2008 May 7. [Epub ahead of print]
Optimal allocation of pandemic influenza vaccine depends on age, risk and timing.
Mylius SD, Hagenaars TJ, Lugn?r AK, Wallinga J. - National Institute for Public Health and the Environment (RIVM), Centre for Infectious Disease Control, Epidemiology and Surveillance Unit, P.O. Box 1, NL ? 3720 BA Bilthoven, The Netherlands.
The limited production capacity for vaccines raises the question what the best strategy is for allocating the vaccine to mitigate an influenza pandemic.
We developed an age-structured model for spread of an influenza pandemic and validated it against observations from the Asian flu pandemic.
Two strategies were evaluated: vaccination can be implemented at the start of the influenza pandemic, or vaccination will be implemented near the peak of it.
Our results suggest prioritizing individuals with a high-risk of complications if a vaccine becomes available during a pandemic.
If available at the start, vaccinating school children might be considered since this results in slightly lower expected number of deaths.
PMID: 18524428 [PubMed - as supplied by publisher]
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(1.13): Vaccine. 2008 May 15. [Epub ahead of print]
Antibody and T-cell responses to a virosomal adjuvanted H9N2 avian influenza vaccine: Impact of distinct additional adjuvants.
Rado?ević K, Rodriguez A, Mintardjo R, Tax D, Bengtsson KL, Thompson C, Zambon M, Weverling GJ, Uytdehaag F, Goudsmit J. - Crucell Holland BV, Leiden, The Netherlands.
A highly efficacious vaccine is required to counteract a threat of an avian influenza pandemic.
Increasing the potency of vaccines by adjuvation is essential not only to overcome generally low immunogenicity of pandemic strains, but also to allow dose sparing and as such to make it feasible to satisfy huge global production demands.
In this study we evaluated the ability of four distinct adjuvants to further increase immune responses to a virosomal adjuvanted avian H9N2 influenza vaccine in mice.
Currently registered adjuvants aluminium phosphate, aluminium hydroxide and MF59, as well as a novel promising adjuvant MATRIX-M were included in the study.
Our results demonstrate that all adjuvants significantly increased the H9N2 haemagglutinin (HA) inhibition and ELISA antibody titers induced with the virosomal adjuvanted vaccine.
The adjuvants exhibited different effect on the isotype of virus specific antibodies, with MATRIX-M inducing the most pronounced skewing to IgG2a, i.e. towards Th1 type of response.
While the virosomal adjuvanted pandemic influenza vaccine efficiently induced CD4(+) T-cell response, with no further increase upon adjuvation, the CD8(+) T-cell responses induced with virosomal adjuvanted vaccine could be significantly improved upon additional adjuvation with MATRIX-M or MF59.
All adjuvants demonstrated a dose sparing effect, i.e. in combination with the virosomal adjuvanted pandemic influenza vaccine they increased immune responses to comparable level independent of the tested vaccine dose.
In conclusion, our results demonstrate that immune responses to a virosomal adjuvanted pandemic influenza vaccine can be further enhanced by add-on adjuvants, with MATRIX-M being overall the most potent adjuvant in combination with virosomes, followed by MF59 and finally aluminium-based adjuvants.
PMID: 18514980 [PubMed - as supplied by publisher]
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(1.14): Vaccine. 2008 May 9. [Epub ahead of print]
Report of the 4th meeting on the "Evaluation of pandemic influenza prototype vaccines in clinical trials"
World Health Organization, Geneva, Switzerland, 14-15 February 2008.
Girard M, Palkonyay L, Kieny MP. - University Paris-Diderot, Lyon, France.
PMID: 18514979 [PubMed - as supplied by publisher]
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(1.15): Vaccine. 2008 May 12. [Epub ahead of print]
Development of a universal influenza A vaccine based on the M2e peptide fused to the papaya mosaic virus (PapMV) vaccine platform.
Denis J, Acosta-Ramirez E, Zhao Y, Hamelin ME, Koukavica I, Baz M, Abed Y, Savard C, Pare C, Lopez Macias C, Boivin G, Leclerc D. - Centre de Recherche en Infectiologie, Pavillon CHUL, Universit? Laval, 2705 boulevard Laurier, Qu?bec, PQ, G1V 4G2 Canada.
With the emergence of highly virulent influenza viruses and the consequent risk of pandemics, new approaches to designing universal influenza vaccines are urgently needed.
In this report, we demonstrate the potential of using a papaya mosaic virus (PapMV) platform carrying the universal M2e influenza epitope (PapMV-CP-M2e) as a candidate flu vaccine.
We show that PapMV-CP-M2e virus-like particles (VLPs) can induce production in mice of anti-M2e antibodies that can recognize influenza-infected cells.
PapMV-CP-M2e discs made of 20 coat protein (CP) subunits were shown to be poorly immunogenic compared to PapMV-CP-M2e VLPs composed of several hundred CP subunits.
We also show that addition of either alum or PapMV-CP VLPs as adjuvant dramatically increased the immunogenicity of PapMV-CP-M2e-containing vaccine, and led to 100% protection against a challenge of 4LD(50) with the WSN/33 strain.
These results show, for the first time, the potential of a recombinant plant virus protein to serve as both peptide delivery system and adjuvant in the crucial field of influenza vaccine development.
PMID: 18511159 [PubMed - as supplied by publisher]
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(1.16): Pediatrics. 2008 May;121(5):e1190-5. Epub 2008 Apr 14.
Nasal continuous positive airway pressure with heliox versus air oxygen in infants with acute bronchiolitis: a crossover study.
Martin?n-Torres F, Rodr?guez-N??ez A, Martin?n-S?nchez JM. - Pediatric Emergency and Critical Care Division, Department of Pediatrics, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain. federico.martinon.torres@sergas.es
OBJECTIVE:
The purpose of this work was to evaluate the effects of administering either heliox or air oxygen in combination with nasal continuous positive airway pressure in infants with refractory bronchiolitis.
PATIENT AND METHODS:
We conducted a prospective, interventional, single-center, crossover study in a teaching hospital including infants 1 month to 2 years of age, consecutively admitted to the PICU from February 2004 to February 2005 for treatment of severe acute bronchiolitis unresponsive to therapy. Patients with a clinical score (Modified Wood's Clinical Asthma Score) of >5, arterial oxygen saturation of <92%, or transcutaneous CO(2) pressure of >50 mmHg despite supportive therapy, nebulized L-epinephrine, and heliox therapy through a nonrebreathing reservoir face mask were eligible. During the study period, 40 infants with bronchiolitis were admitted to the PICU; 12 fulfilled inclusion criteria. A predetermined balanced sequential allocation to either 30 minutes of treatment with nasal continuous positive airway pressure with heliox or to air-oxygen nasal continuous positive airway pressure was performed. Measurements were taken at baseline and after 30 minutes of each treatment.
RESULTS:
Baseline mean values were as follows: nasal continuous positive airway pressure of 7.2 cmH(2)O; clinical score of 7.7 points; transcutaneous CO(2) pressure of 61.6 mmHg; and arterial oxygen saturation of 88.6%, with the fraction of inspired oxygen at 35.4%. Clinical score, transcutaneous CO(2) pressure, and arterial oxygen saturation improved during the study time with both heliox-nasal continuous positive airway pressure and air-oxygen-nasal continuous positive airway pressure: after 1 hour, the clinical score fell 1.7 points, transcutaneous CO(2) pressure decreased 8.2 mmHg, and arterial oxygen saturation increased by 7.7%. Improvement in clinical score was double with heliox-nasal continuous positive airway pressure compared with the air-oxygen-nasal continuous positive airway pressure (2.12 vs 1.08 points), and the fall in the transcutaneous CO(2) pressure was greater with heliox-nasal continuous positive airway pressure compared with air-oxygen-nasal continuous positive airway pressure (9.7 vs 5.4 mm Hg). There was no difference in arterial oxygen saturation between groups. No patients required endotracheal intubation. No adverse effects attributable to either of the study interventions were detected.
CONCLUSIONS:
Nasal continuous positive airway pressure improves the clinical score and the CO(2) elimination of infants with refractory bronchiolitis. These positive effects are significantly enhanced when nasal continuous positive airway pressure is combined with heliox instead of air oxygen. Both techniques are noninvasive, seem safe, and may reduce the need for endotracheal intubation.
PMID: 18411235 [PubMed - indexed for MEDLINE]
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Contents:
(1.1) Prospective evaluation of rapid antigen tests for diagnosis of respiratory syncytial virus and human metapneumovirus infections.
(1.2) Identifying infections with respiratory syncytial virus by using specific immunoglobulin G (IgG) and IgA enzyme-linked immunosorbent assays with oral-fluid samples.
(1.3) Anti-Ganglioside Antibody Induction by Swine (A/NJ/1976/H1N1) and Other Influenza Vaccines: Insights into Vaccine-Associated Guillain-Barr? Syndrome.
(1.4) Prevention of Symptomatic Seasonal Influenza in 2005-2006 by Inactivated and Live Attenuated Vaccines.
(1.5) Plasmid DNA-Based Vaccines Protect Mice and Ferrets against Lethal Challenge with A/Vietnam/1203/04 (H5N1) Influenza Virus
(1.6) Influenza virus infection augments NK cell inhibition through the reorganization of MHC class I proteins.
(1.7) The role of interferon in the replication of human parainfluenza virus type 1 wild type and mutant viruses in human ciliated airway epithelium.
(1.8) Acute lower respiratory tract infection.
(1.9) Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus.
(1.10) High titer growth of human and avian influenza viruses in an immortalized chick embryo cell line without the need for exogenous proteases.
(1.11) The effectiveness of national influenza vaccination policies for at-risk populations over 5 seasons in a Scottish general practice.
(1.12) Optimal allocation of pandemic influenza vaccine depends on age, risk and timing.
(1.13) Antibody and T-cell responses to a virosomal adjuvanted H9N2 avian influenza vaccine: Impact of distinct additional adjuvants.
(1.14) Report of the 4th meeting on the "Evaluation of pandemic influenza prototype vaccines in clinical trials"
(1.15) Development of a universal influenza A vaccine based on the M2e peptide fused to the papaya mosaic virus (PapMV) vaccine platform.
(1.16) Nasal continuous positive airway pressure with heliox versus air oxygen in infants with acute bronchiolitis: a crossover study.
See original abstracts at the source site. EDITED.]
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(1.1): J Clin Microbiol. 2008 May;46(5):1682-5. Epub 2008 Mar 12.
Prospective evaluation of rapid antigen tests for diagnosis of respiratory syncytial virus and human metapneumovirus infections.
Aslanzadeh J, Zheng X, Li H, Tetreault J, Ratkiewicz I, Meng S, Hamilton P, Tang YW. - Hartford Hospital and Clinical Laboratory Partners, Hartford, Connecticut 06102, USA. Jaslanz@harthosp.org
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two important viral pathogens that cause respiratory tract infections in the pediatric population.
The rapid detection of these agents allows the prompt isolation and treatment of infected patients.
In the present prospective study, we evaluated the performances of four rapid antigen detection assays, including a rapid chromatographic immunoassay (CIA) for RSV (Directigen EZ RSV; Becton Dickinson, Sparks, MD), a direct fluorescent-antibody assay (DFA) for RSV (Bartels; Trinity Biotech, Carlsbad, CA), and two DFAs for hMPV manufactured by Diagnostic Hybrids Inc. (DHI; Athens, OH) and Imagen (Oxoid Ltd., Basingstoke, Hampshire, United Kingdom).
The clinical specimens tested comprised 515 nasopharyngeal aspirates submitted to the Clinical Microbiology Laboratory at Hartford Hospital from 1 November 2006 to 21 April 2007.
Compared to the results of real-time reverse transcription-PCR (RT-PCR), the CIA had a sensitivity of 79.8% and a specificity of 89.5%.
The RSV DFA with Bartels reagents showed a sensitivity of 94.1% and a specificity of 96.8%.
For hMPV, the sensitivity and specificity were 62.5% and 99.8%, respectively, for the DHI DFA and 63.2% and 100%, respectively, for the Imagen DFA.
The hands-on and test turnaround times for CIA were 10 and 30 to 60 min, respectively, and the hands-on and test turnaround times for the RSV and hMPV DFAs were 30 and 105 min, respectively.
We conclude that while the RSV CIA is user-friendly, it lacks sensitivity and specificity, especially during off-peak months. In contrast, the RSV DFA is more sensitive and specific, but interpretation of its results is subjective and it demands technical time and expertise.
Similarly, both hMPV DFAs are highly specific in comparison to the results of RT-PCR, but their sensitivities await further improvements.
PMID: 18337386 [PubMed - indexed for MEDLINE] - PMCID: PMC2395112 [Available on 09/01/08]
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(1.2): J Clin Microbiol. 2008 May;46(5):1659-62. Epub 2008 Feb 27.
Identifying infections with respiratory syncytial virus by using specific immunoglobulin G (IgG) and IgA enzyme-linked immunosorbent assays with oral-fluid samples.
Okiro EA, Sande C, Mutunga M, Medley GF, Cane PA, Nokes DJ. - Centre for Geographic Medicine Research--Coast, Kenya Medical Research Institute/Wellcome Trust Research Programme, Kilifi, Kenya. eokiro@nairobi.kemri-wellcome.org
Currently, respiratory syncytial virus (RSV) infection is identified in epidemiological studies by virus antigen or nucleic acid detection in combination with serology.
Oral-fluid specimens may provide a noninvasive alternative to blood, and oral fluid is more suitable for sampling outside of the clinic setting.
We evaluated an indirect enzyme-linked immunosorbent assay for the detection of RSV-specific immunoglobulin G (IgG) and IgA by using oral-fluid samples collected from individuals with RSV infections confirmed by an immunofluorescent antibody test.
For five children sampled repeatedly from birth, antibody profiles in oral fluid quite consistently tracked those in paired sera, and RSV infections were detected by rising titers of antibodies of at least one Ig class.
Specific IgG responses were generally more reliable than IgA responses, except in early infancy, where the reverse was sometimes true.
For a further five young children from whom oral fluid was collected weekly following RSV infection, boosted antibody responses, frequently of a transient nature, lasting a few weeks, were observed; specific IgG responses were of longer duration and more pronounced than specific IgA responses.
Our data show significant promise for the use of oral fluid alone in RSV infection surveillance.
The observed rapid dynamics of the antibody responses are informative in defining study sampling intervals.
PMID: 18305129 [PubMed - indexed for MEDLINE] - PMCID: PMC2395083 [Available on 09/01/08]
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(1.3): J Infect Dis. 2008 Jun 3. [Epub ahead of print]
Anti-Ganglioside Antibody Induction by Swine (A/NJ/1976/H1N1) and Other Influenza Vaccines: Insights into Vaccine-Associated Guillain-Barr? Syndrome.
Nachamkin I, Shadomy SV, Moran AP, Cox N, Fitzgerald C, Ung H, Corcoran AT, Iskander JK, Schonberger LB, Chen RT. - 1Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia; 2Centers for Disease Control and Prevention, Atlanta, Georgia; 3Department of Microbiology, National University of Ireland, Galway.
Background.
Receipt of an A/NJ/1976/H1N1 "swine flu" vaccine in 1976, unlike receipt of influenza vaccines used in subsequent years, was strongly associated with the development of the neurologic disorder Guillain-Barr? syndrome (GBS). Anti-ganglioside antibodies (e.g., anti-GM(1)) are associated with the development of GBS, and we hypothesized that the swine flu vaccine contained contaminating moieties (such as Campylobacter jejuni antigens that mimic human gangliosides or other vaccine components) that elicited an anti-GM(1) antibody response in susceptible recipients.
Methods
Surviving samples of monovalent and bivalent 1976 vaccine, comprising those from 3 manufacturers and 11 lot numbers, along with several contemporary vaccines were tested for hemagglutinin (HA) activity, the presence of Campylobacter DNA, and the ability to induce anti-Campylobacter and anti-GM(1) antibodies after inoculation into C3H/HeN mice.
Results.
We found that, although C. jejuni was not detected in 1976 swine flu vaccines, these vaccines induced anti-GM(1) antibodies in mice, as did vaccines from 1991-1992 and 2004-2005. Preliminary studies suggest that the influenza HA induces anti-GM(1) antibodies.
Conclusions.
Influenza vaccines contain structures that can induce anti-GM(1) antibodies after inoculation into mice. Further research into influenza vaccine components that elicit anti-ganglioside responses and the role played by these antibodies (if any) in vaccine-associated GBS is warranted.
PMID: 18522505 [PubMed - as supplied by publisher]
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(1.4): J Infect Dis. 2008 Jun 3. [Epub ahead of print]
Prevention of Symptomatic Seasonal Influenza in 2005-2006 by Inactivated and Live Attenuated Vaccines.
Ohmit SE, Victor JC, Teich ER, Truscon RK, Rotthoff JR, Newton DW, Campbell SA, Boulton ML, Monto AS. - 1University of Michigan School of Public Health, Department of Epidemiology, 2University of Michigan Hospitals, Department of Pathology, Ann Arbor, 3Central Michigan University Health Services, Mount Pleasant, Michigan; 4Program for Appropriate Technology in Health, Seattle, Washington.
Background.
The efficacy of influenza vaccines may vary annually. In 2004-2005, when antigenically drifted viruses were circulating, a randomized, placebo-controlled trial involving healthy adults showed that inactivated vaccine appeared to be efficacious, whereas live attenuated vaccine appeared to be less so.
Methods.
In 2005-2006, we continued our trial, examining the absolute and relative efficacies of the live attenuated and inactivated vaccines in preventing laboratory-confirmed symptomatic influenza.
Results.
A total of 2058 persons were vaccinated in October and November 2005. Studywide influenza activity was prolonged but of low intensity; type A (H3N2) virus was circulating, which was antigenically similar to the vaccine strain. The absolute efficacy of the inactivated vaccine was 16% (95% confidence interval [CI], -171% to 70%) for the virus identification end point (virus isolation in cell culture or identification through polymerase chain reaction) and 54% (95% CI, 4%-77%) for the primary end point (virus isolation or increase in serum antibody titer). The absolute efficacies of the live attenuated vaccine for these end points were 8% (95% CI, -194% to 67%) and 43% (95% CI, -15% to 71%), respectively.
Conclusions.
With serologic end points included, efficacy was demonstrated for the inactivated vaccine in a year with low influenza attack rates. The efficacy of the live attenuated vaccine was slightly less than that of the inactivated vaccine, but not statistically greater than that of the placebo. Trial registration. ClinicalTrials.gov identifier: NCT00133523 .
PMID: 18522501 [PubMed - as supplied by publisher]
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(1.5): J Infect Dis. 2008 Jun 15;197(12):1643-1652.
Plasmid DNA-Based Vaccines Protect Mice and Ferrets against Lethal Challenge with A/Vietnam/1203/04 (H5N1) Influenza Virus.
Lalor PA, Webby RJ, Morrow J, Rusalov D, Kaslow DC, Rolland A, Smith LR. - 1Vical, Inc., San Diego, California; 2Division of Virology, Department of Infectious Diseases, St. Jude Children?s Research Hospital, Memphis, Tennessee.
Plasmid DNA (pDNA) vaccines represent an alternative to conventional inactivated influenza vaccines that are likely to experience supply constraints during a pandemic.
Several Vaxfectin-formulated pDNA vaccines were tested in mice and ferrets for efficacy against a lethal challenge with the highly pathogenic A/Vietnam/1203/04 (H5N1) influenza virus strain; the vaccines encoded influenza A virus hemagglutinin (HA), and/or nucleoprotein (NP), and M2 protein.
Complete protection from death and disease was achieved in mice and ferrets with 2 doses of a Vaxfectin-formulated vaccine containing H5 HA, NP, and M2 plasmids and in ferrets with only 1 dose.
A Vaxfectin-formulated vaccine containing NP and M2 pDNA provided significant protection against death in mice and provided some benefit in ferrets (i.e., 17% survival, delayed time to illness and death, and significant reduction in viral load compared with that in negative control animals).
These experiments support the clinical testing of pDNA vaccine candidates that may ultimately increase global vaccine supply options during pandemics.
PMID: 18513153 [PubMed - as supplied by publisher
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(1.6): J Virol. 2008 Jun 4. [Epub ahead of print]
Influenza virus infection augments NK cell inhibition through the reorganization of MHC class I proteins.
Achdout H, Manaster I, Mandelboim O. - The Lautenberg Center for General and Tumor Immunology, the Hebrew University Hadassah Medical School, Jerusalem, 91120, Israel.
The killing by Natural Killer (NK) cells is regulated by inhibitory, costimulatory and activating receptors.
The inhibitory receptors recognize mainly MHC class I molecules, while the activating NK receptors recognize stress induced ligands and viral products.
Thus, changes in the expression of the various inhibitory and activating ligands will determine whether target cells will be killed or protected.
Here we demonstrate that following influenza infection the binding of the two NK inhibitory receptors; KIR2DL1 and the LIR1 to the infected cells is specifically increased.
The increased binding occurs shortly after the influenza infection, prior to the increased recognition of the infected cells by the NK activating receptor, NKp46.
We also elucidate the mechanism responsible for this effect and demonstrate that following influenza virus infection, MHC class I proteins redistribute on the cell surface and accumulate in the lipid rafts microdomains.
Such redistribution allows better recognition by NK inhibitory receptors and consequently increases resistance to NK cell attack.
In contrast, T cell activity was not influenced by the redistribution of MHC class I proteins.
Thus, we present here a novel mechanism, developed by the influenza virus, of inhibition of NK cell cytotoxicity, through the reorganization of MHC class I proteins on the cell surface.
PMID: 18524833 [PubMed - as supplied by publisher]
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(1.7): J Virol. 2008 Jun 4. [Epub ahead of print]
The role of interferon in the replication of human parainfluenza virus type 1 wild type and mutant viruses in human ciliated airway epithelium.
Bartlett EJ, Hennessey M, Skiadopoulos MH, Schmidt AC, Collins PL, Murphy BR, Pickles RJ. - Laboratory of Infectious Diseases, Respiratory Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services. Bethesda, MD, 20892-2007, USA; Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill. Chapel Hill, NC, 27599-7248, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill. Chapel Hill, NC, 27599-7248, USA.
Human parainfluenza virus type 1 (HPIV1) is a significant cause of pediatric respiratory disease, in the upper and lower airways.
An in vitro model of human ciliated airway epithelium (HAE), a useful tool for studying respiratory virus-host interactions, was used in this study to show that HPIV1 selectively infects ciliated cells within the HAE and that progeny virus is released from the apical surface with little apparent gross cytopathology.
In HAE, type I interferon (IFN) is induced following infection with a HPIV1 mutant expressing defective C proteins with a F170S amino acid substitution, rHPIV1-C(F170S), but not following infection with HPIV1 wild type (wt).
IFN induction coincided with a 100 to 1000-fold reduction in virus titer, supporting the hypothesis that the HPIV1 C proteins are critical for inhibition of the innate immune response.
Two recently characterized live attenuated HPIV1 vaccine candidates expressing mutant C proteins were also evaluated in HAE.
The vaccine candidates, rHPIV1-C(R84G/Delta170)HN(T553A)L(Y942A) and rHPIV1-C(R84G/Delta170)HN(T553A)L(Delta1710-11), which contain temperature sensitive (ts) attenuating (att) and non-ts att mutations, were highly restricted in growth in HAE at permissive (32 degrees C) and restrictive (37 degrees C) temperatures.
The viruses grew slightly better at 37 degrees C than at 32 degrees C, and rHPIV1-C(R84G/Delta170)HN(T553A)L(Y942A) was less attenuated than rHPIV1-C(R84G/Delta170)HN(T553A)L(Delta1710-11).
The level of replication in HAE correlated with that previously observed in African green monkeys, suggesting that the HAE model has potential as a tool for pre-clinical evaluation of HPIV1 vaccines, although how these in vitro data will correlate with vaccine virus replication in seronegative human subjects remains to be seen.
PMID: 18524813 [PubMed - as supplied by publisher]
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(1.8): N Engl J Med. 2008 May 29;358(22):2413-4; author reply 2414.
Comment on: N Engl J Med. 2008 Feb 14;358(7):716-27.
Acute lower respiratory tract infection.
Eisenhut M.
PMID: 18509133 [PubMed - indexed for MEDLINE]
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(1.9): Proc Natl Acad Sci U S A. 2008 Jun 3. [Epub ahead of print]
Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus.
Zheng BJ, Chan KW, Lin YP, Zhao GY, Chan C, Zhang HJ, Chen HL, Wong SS, Lau SK, Woo PC, Chan KH, Jin DY, Yuen KY. - State Key Laboratory of Emerging Infectious Diseases.
The mortality of human infection by influenza A/H5N1 virus can exceed 80%.
The high mortality and its poor response to the neuraminidase inhibitor oseltamivir have been attributed to uncontrolled virus-induced cytokine storm.
We challenged BALB/c mice with 1,000 LD(50) of influenza A/Vietnam/1194/04.
Survival, body weight, histopathology, inflammatory markers, viral loads, T lymphocyte counts, and neutralizing antibody response were documented in infected mice treated individually or in combination with zanamvir, celecoxib, gemfibrozil, and mesalazine.
To imitate the real-life scenario, treatment was initiated at 48 h after viral challenge.
There were significant improvements in survival rate (P = 0.02), survival time (P < 0.02), and inflammatory markers (P < 0.01) in the group treated with a triple combination of zanamivir, celecoxib, and mesalazine when compared with zanamivir alone.
Zanamivir with or without immunomodulators reduced viral load to a similar extent.
Insignificant prolongation of survival was observed when individual agents were used alone.
Significantly higher levels of CD4(+) and CD8(+) T lymphocytes and less pulmonary inflammation were also found in the group receiving triple therapy.
Zanamivir alone reduced viral load but not inflammation and mortality.
The survival benefits of adding celecoxib and mesalazine to zanamivir could be caused by their synergistic effects in reducing cytokine dysfunction and preventing apoptosis.
Combinations of a neuraminidase inhibitor with these immunomodulators should be considered in randomized controlled treatment trials of patients suffering from H5N1 infection.
PMID: 18523003 [PubMed - as supplied by publisher
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(1.10): Vaccine. 2008 May 8. [Epub ahead of print]
High titer growth of human and avian influenza viruses in an immortalized chick embryo cell line without the need for exogenous proteases.
Smith KA, Colvin CJ, Weber PS, Spatz SJ, Coussens PM. - Molecular Pathogenesis Laboratory, Department of Animal Science, Michigan State, University, East Lansing, Michigan, USA.
The current method of growing influenza virus for vaccine production is through the use of embryonated chicken eggs.
This manufacturing system yields a low concentration of virus per egg, requires significant downstream production for purification, and demands a considerable amount of time for production.
We have demonstrated an immortalized chick embryo cell line, termed PBS-1, is capable of growing unmodified recent isolates of human and avian influenza A and B viruses to extremely high titers.
In many cases, PBS-1 cells out perform primary chick embryo kidney (CEK) cells, Madin-Darby Canine Kidney (MDCK) cells and African green monkey kidney cells (Vero) in growth of recent influenza isolates.
PBS-1 cells are free of any exogenous agents, are non-tumorigenic, and are readily adaptable to a variety of culture conditions, including growth on microcarrier beads.
Influenza viruses grown in PBS-1 cells are released into the culture fluid without the need for exogenous proteases, thus simplifying downstream processing.
In addition to offering a significant improvement in vaccine production, PBS-1 cells should prove valuable in diagnostics and as a cell line of choice for influenza virus research.
PMID: 18524432 [PubMed - as supplied by publisher]
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(1.11): Vaccine. 2008 May 5. [Epub ahead of print]
The effectiveness of national influenza vaccination policies for at-risk populations over 5 seasons in a Scottish general practice.
Sivaprakasam V, Douglas J, Selvaraj S, Macintyre S, Carman WF. - West of Scotland Specialist Virology Centre, Glasgow, Scotland, UK.
AIM:
To determine the effectiveness of serial influenza vaccination.
SCOPE:
Studied in a Scottish GP population, the overall seroresponse rate increased with annual influenza vaccinations and after 5 years it increased from 45.1% to 93.3% for influenza virus A (H1) and from 48.4% to 98.3% for influenza virus A (H3). However, there was little boosting effect with further doses after becoming a seroresponder. The pre-vaccination titres were significantly higher in previous year's seroresponders compared to non-responders.
CONCLUSIONS:
The policy of annual vaccination is supported by our data in order to increase the disappointing response rate after one dose. However, the lack of a boosting response with subsequent doses and the significant residual immunity after becoming a seroresponder suggests a prior serological immunity check in order to better direct the vaccine supply (in the years of no antigenic drift), to those who need it most.
PMID: 18524431 [PubMed - as supplied by publisher]
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(1.12): Vaccine. 2008 May 7. [Epub ahead of print]
Optimal allocation of pandemic influenza vaccine depends on age, risk and timing.
Mylius SD, Hagenaars TJ, Lugn?r AK, Wallinga J. - National Institute for Public Health and the Environment (RIVM), Centre for Infectious Disease Control, Epidemiology and Surveillance Unit, P.O. Box 1, NL ? 3720 BA Bilthoven, The Netherlands.
The limited production capacity for vaccines raises the question what the best strategy is for allocating the vaccine to mitigate an influenza pandemic.
We developed an age-structured model for spread of an influenza pandemic and validated it against observations from the Asian flu pandemic.
Two strategies were evaluated: vaccination can be implemented at the start of the influenza pandemic, or vaccination will be implemented near the peak of it.
Our results suggest prioritizing individuals with a high-risk of complications if a vaccine becomes available during a pandemic.
If available at the start, vaccinating school children might be considered since this results in slightly lower expected number of deaths.
PMID: 18524428 [PubMed - as supplied by publisher]
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(1.13): Vaccine. 2008 May 15. [Epub ahead of print]
Antibody and T-cell responses to a virosomal adjuvanted H9N2 avian influenza vaccine: Impact of distinct additional adjuvants.
Rado?ević K, Rodriguez A, Mintardjo R, Tax D, Bengtsson KL, Thompson C, Zambon M, Weverling GJ, Uytdehaag F, Goudsmit J. - Crucell Holland BV, Leiden, The Netherlands.
A highly efficacious vaccine is required to counteract a threat of an avian influenza pandemic.
Increasing the potency of vaccines by adjuvation is essential not only to overcome generally low immunogenicity of pandemic strains, but also to allow dose sparing and as such to make it feasible to satisfy huge global production demands.
In this study we evaluated the ability of four distinct adjuvants to further increase immune responses to a virosomal adjuvanted avian H9N2 influenza vaccine in mice.
Currently registered adjuvants aluminium phosphate, aluminium hydroxide and MF59, as well as a novel promising adjuvant MATRIX-M were included in the study.
Our results demonstrate that all adjuvants significantly increased the H9N2 haemagglutinin (HA) inhibition and ELISA antibody titers induced with the virosomal adjuvanted vaccine.
The adjuvants exhibited different effect on the isotype of virus specific antibodies, with MATRIX-M inducing the most pronounced skewing to IgG2a, i.e. towards Th1 type of response.
While the virosomal adjuvanted pandemic influenza vaccine efficiently induced CD4(+) T-cell response, with no further increase upon adjuvation, the CD8(+) T-cell responses induced with virosomal adjuvanted vaccine could be significantly improved upon additional adjuvation with MATRIX-M or MF59.
All adjuvants demonstrated a dose sparing effect, i.e. in combination with the virosomal adjuvanted pandemic influenza vaccine they increased immune responses to comparable level independent of the tested vaccine dose.
In conclusion, our results demonstrate that immune responses to a virosomal adjuvanted pandemic influenza vaccine can be further enhanced by add-on adjuvants, with MATRIX-M being overall the most potent adjuvant in combination with virosomes, followed by MF59 and finally aluminium-based adjuvants.
PMID: 18514980 [PubMed - as supplied by publisher]
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(1.14): Vaccine. 2008 May 9. [Epub ahead of print]
Report of the 4th meeting on the "Evaluation of pandemic influenza prototype vaccines in clinical trials"
World Health Organization, Geneva, Switzerland, 14-15 February 2008.
Girard M, Palkonyay L, Kieny MP. - University Paris-Diderot, Lyon, France.
PMID: 18514979 [PubMed - as supplied by publisher]
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(1.15): Vaccine. 2008 May 12. [Epub ahead of print]
Development of a universal influenza A vaccine based on the M2e peptide fused to the papaya mosaic virus (PapMV) vaccine platform.
Denis J, Acosta-Ramirez E, Zhao Y, Hamelin ME, Koukavica I, Baz M, Abed Y, Savard C, Pare C, Lopez Macias C, Boivin G, Leclerc D. - Centre de Recherche en Infectiologie, Pavillon CHUL, Universit? Laval, 2705 boulevard Laurier, Qu?bec, PQ, G1V 4G2 Canada.
With the emergence of highly virulent influenza viruses and the consequent risk of pandemics, new approaches to designing universal influenza vaccines are urgently needed.
In this report, we demonstrate the potential of using a papaya mosaic virus (PapMV) platform carrying the universal M2e influenza epitope (PapMV-CP-M2e) as a candidate flu vaccine.
We show that PapMV-CP-M2e virus-like particles (VLPs) can induce production in mice of anti-M2e antibodies that can recognize influenza-infected cells.
PapMV-CP-M2e discs made of 20 coat protein (CP) subunits were shown to be poorly immunogenic compared to PapMV-CP-M2e VLPs composed of several hundred CP subunits.
We also show that addition of either alum or PapMV-CP VLPs as adjuvant dramatically increased the immunogenicity of PapMV-CP-M2e-containing vaccine, and led to 100% protection against a challenge of 4LD(50) with the WSN/33 strain.
These results show, for the first time, the potential of a recombinant plant virus protein to serve as both peptide delivery system and adjuvant in the crucial field of influenza vaccine development.
PMID: 18511159 [PubMed - as supplied by publisher]
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(1.16): Pediatrics. 2008 May;121(5):e1190-5. Epub 2008 Apr 14.
Nasal continuous positive airway pressure with heliox versus air oxygen in infants with acute bronchiolitis: a crossover study.
Martin?n-Torres F, Rodr?guez-N??ez A, Martin?n-S?nchez JM. - Pediatric Emergency and Critical Care Division, Department of Pediatrics, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain. federico.martinon.torres@sergas.es
OBJECTIVE:
The purpose of this work was to evaluate the effects of administering either heliox or air oxygen in combination with nasal continuous positive airway pressure in infants with refractory bronchiolitis.
PATIENT AND METHODS:
We conducted a prospective, interventional, single-center, crossover study in a teaching hospital including infants 1 month to 2 years of age, consecutively admitted to the PICU from February 2004 to February 2005 for treatment of severe acute bronchiolitis unresponsive to therapy. Patients with a clinical score (Modified Wood's Clinical Asthma Score) of >5, arterial oxygen saturation of <92%, or transcutaneous CO(2) pressure of >50 mmHg despite supportive therapy, nebulized L-epinephrine, and heliox therapy through a nonrebreathing reservoir face mask were eligible. During the study period, 40 infants with bronchiolitis were admitted to the PICU; 12 fulfilled inclusion criteria. A predetermined balanced sequential allocation to either 30 minutes of treatment with nasal continuous positive airway pressure with heliox or to air-oxygen nasal continuous positive airway pressure was performed. Measurements were taken at baseline and after 30 minutes of each treatment.
RESULTS:
Baseline mean values were as follows: nasal continuous positive airway pressure of 7.2 cmH(2)O; clinical score of 7.7 points; transcutaneous CO(2) pressure of 61.6 mmHg; and arterial oxygen saturation of 88.6%, with the fraction of inspired oxygen at 35.4%. Clinical score, transcutaneous CO(2) pressure, and arterial oxygen saturation improved during the study time with both heliox-nasal continuous positive airway pressure and air-oxygen-nasal continuous positive airway pressure: after 1 hour, the clinical score fell 1.7 points, transcutaneous CO(2) pressure decreased 8.2 mmHg, and arterial oxygen saturation increased by 7.7%. Improvement in clinical score was double with heliox-nasal continuous positive airway pressure compared with the air-oxygen-nasal continuous positive airway pressure (2.12 vs 1.08 points), and the fall in the transcutaneous CO(2) pressure was greater with heliox-nasal continuous positive airway pressure compared with air-oxygen-nasal continuous positive airway pressure (9.7 vs 5.4 mm Hg). There was no difference in arterial oxygen saturation between groups. No patients required endotracheal intubation. No adverse effects attributable to either of the study interventions were detected.
CONCLUSIONS:
Nasal continuous positive airway pressure improves the clinical score and the CO(2) elimination of infants with refractory bronchiolitis. These positive effects are significantly enhanced when nasal continuous positive airway pressure is combined with heliox instead of air oxygen. Both techniques are noninvasive, seem safe, and may reduce the need for endotracheal intubation.
PMID: 18411235 [PubMed - indexed for MEDLINE]
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