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A computationally optimized hemagglutinin virus-like particle vaccine elicits broadly reactive antibodies that protect nonhuman primates from H5N1 infection.
J Infect Dis. 2012 May 15; 205(10):1562-70.JI

Abstract

BACKGROUND

Highly pathogenic H5N1 avian influenza viruses continue to spread via waterfowl, causing lethal infections in humans. Vaccines can prevent the morbidity and mortality associated with pandemic influenza isolates. Predicting the specific isolate that may emerge from the 10 different H5N1 clades is a tremendous challenge for vaccine design.

METHODS

In this study, we generated a synthetic hemagglutinin (HA) on the basis of a new method, computationally optimized broadly reactive antigen (COBRA), which uses worldwide sequencing and surveillance efforts that are specifically focused on sequences from H5N1 clade 2 human isolates.

RESULTS

Cynomolgus macaques vaccinated with COBRA clade 2 HA H5N1 virus-like particles (VLPs) had hemagglutination-inhibition antibody titers that recognized a broader number of representative isolates from divergent clades as compared to nonhuman primates vaccinated with clade 2.2 HA VLPs. Furthermore, all vaccinated animals were protected from A/Whooper Swan/Mongolia/244/2005 (WS/05) clade 2.2 challenge, with no virus detected in the nasal or tracheal washes. However, COBRA VLP-vaccinated nonhuman primates had reduced lung inflammation and pathologic effects as compared to those that received WS/05 VLP vaccines.

CONCLUSIONS

The COBRA clade 2 HA H5N1 VLP elicits broad humoral immunity against multiple H5N1 isolates from different clades. In addition, the COBRA VLP vaccine is more effective than a homologous vaccine against a highly pathogenic avian influenza virus challenge.

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Authors+Show Affiliations

Giles BM
Center for Vaccine Research, University of Pittsburgh, Pennsylvania 15261, USA.
Crevar CJ
No affiliation info available
Carter DM
No affiliation info available
Bissel SJ
No affiliation info available
Schultz-Cherry S
No affiliation info available
Wiley CA
No affiliation info available
Ross TM
No affiliation info available

MeSH

Amino Acid SequenceAnimalsAntibodies, ViralAntigens, ViralCell Line, TransformedComputer-Aided DesignConsensus SequenceDisease Models, AnimalHemagglutinins, ViralHumansInfluenza A Virus, H5N1 SubtypeInfluenza VaccinesInfluenza, HumanLikelihood FunctionsLungMacaca fascicularisMaleOrthomyxoviridae InfectionsPhylogenyVaccinationVaccines, Virus-Like Particle

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22448011

Citation

Giles, Brendan M., et al. "A Computationally Optimized Hemagglutinin Virus-like Particle Vaccine Elicits Broadly Reactive Antibodies That Protect Nonhuman Primates From H5N1 Infection." The Journal of Infectious Diseases, vol. 205, no. 10, 2012, pp. 1562-70.
Giles BM, Crevar CJ, Carter DM, et al. A computationally optimized hemagglutinin virus-like particle vaccine elicits broadly reactive antibodies that protect nonhuman primates from H5N1 infection. J Infect Dis. 2012;205(10):1562-70.
Giles, B. M., Crevar, C. J., Carter, D. M., Bissel, S. J., Schultz-Cherry, S., Wiley, C. A., & Ross, T. M. (2012). A computationally optimized hemagglutinin virus-like particle vaccine elicits broadly reactive antibodies that protect nonhuman primates from H5N1 infection. The Journal of Infectious Diseases, 205(10), 1562-70. https://doi.org/10.1093/infdis/jis232
Giles BM, et al. A Computationally Optimized Hemagglutinin Virus-like Particle Vaccine Elicits Broadly Reactive Antibodies That Protect Nonhuman Primates From H5N1 Infection. J Infect Dis. 2012 May 15;205(10):1562-70. PubMed PMID: 22448011.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A computationally optimized hemagglutinin virus-like particle vaccine elicits broadly reactive antibodies that protect nonhuman primates from H5N1 infection. AU - Giles,Brendan M, AU - Crevar,Corey J, AU - Carter,Donald M, AU - Bissel,Stephanie J, AU - Schultz-Cherry,Stacey, AU - Wiley,Clayton A, AU - Ross,Ted M, Y1 - 2012/03/23/ PY - 2012/3/27/entrez PY - 2012/3/27/pubmed PY - 2012/6/30/medline SP - 1562 EP - 70 JF - The Journal of infectious diseases JO - J Infect Dis VL - 205 IS - 10 N2 - BACKGROUND: Highly pathogenic H5N1 avian influenza viruses continue to spread via waterfowl, causing lethal infections in humans. Vaccines can prevent the morbidity and mortality associated with pandemic influenza isolates. Predicting the specific isolate that may emerge from the 10 different H5N1 clades is a tremendous challenge for vaccine design. METHODS: In this study, we generated a synthetic hemagglutinin (HA) on the basis of a new method, computationally optimized broadly reactive antigen (COBRA), which uses worldwide sequencing and surveillance efforts that are specifically focused on sequences from H5N1 clade 2 human isolates. RESULTS: Cynomolgus macaques vaccinated with COBRA clade 2 HA H5N1 virus-like particles (VLPs) had hemagglutination-inhibition antibody titers that recognized a broader number of representative isolates from divergent clades as compared to nonhuman primates vaccinated with clade 2.2 HA VLPs. Furthermore, all vaccinated animals were protected from A/Whooper Swan/Mongolia/244/2005 (WS/05) clade 2.2 challenge, with no virus detected in the nasal or tracheal washes. However, COBRA VLP-vaccinated nonhuman primates had reduced lung inflammation and pathologic effects as compared to those that received WS/05 VLP vaccines. CONCLUSIONS: The COBRA clade 2 HA H5N1 VLP elicits broad humoral immunity against multiple H5N1 isolates from different clades. In addition, the COBRA VLP vaccine is more effective than a homologous vaccine against a highly pathogenic avian influenza virus challenge. SN - 1537-6613 UR - https://www.unboundmedicine.com/medline/citation/22448011/A_computationally_optimized_hemagglutinin_virus_like_particle_vaccine_elicits_broadly_reactive_antibodies_that_protect_nonhuman_primates_from_H5N1_infection_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1093/infdis/jis232 DB - PRIME DP - Unbound Medicine ER -