A Computationally Optimized Hemagglutinin Virus-like Particle Vaccine Elicits Broadly Reactive Antibodies That Protect Nonhuman Primates from H5N1 Infection

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2012 Mar 27

PMID 22448011

Citations 65

Authors

Brendan M Giles

Corey J Crevar

Donald M Carter

Stephanie J Bissel

Stacey Schultz-Cherry

Clayton A Wiley

Ted M Ross

Affiliations

Soon will be listed here.

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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References

Bao Y, Bolotov P, Dernovoy D, Kiryutin B, Zaslavsky L, Tatusova T . The influenza virus resource at the National Center for Biotechnology Information. J Virol. 2007; 82(2):596-601. PMC: 2224563. DOI: 10.1128/JVI.02005-07. View

Pushko P, Pearce M, Ahmad A, Tretyakova I, Smith G, Belser J . Influenza virus-like particle can accommodate multiple subtypes of hemagglutinin and protect from multiple influenza types and subtypes. Vaccine. 2011; 29(35):5911-8. DOI: 10.1016/j.vaccine.2011.06.068. View

Dereeper A, Guignon V, Blanc G, Audic S, Buffet S, Chevenet F . Phylogeny.fr: robust phylogenetic analysis for the non-specialist. Nucleic Acids Res. 2008; 36(Web Server issue):W465-9. PMC: 2447785. DOI: 10.1093/nar/gkn180. View

Fan S, Gao Y, Shinya K, Li C, Li Y, Shi J . Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates. PLoS Pathog. 2009; 5(5):e1000409. PMC: 2669169. DOI: 10.1371/journal.ppat.1000409. View

Salzberg S, Kingsford C, Cattoli G, Spiro D, Janies D, Aly M . Genome analysis linking recent European and African influenza (H5N1) viruses. Emerg Infect Dis. 2007; 13(5):713-8. PMC: 2432181. DOI: 10.3201/eid1305.070013. View

Steel J, Lowen A, Wang T, Yondola M, Gao Q, Haye K . Influenza virus vaccine based on the conserved hemagglutinin stalk domain. mBio. 2010; 1(1). PMC: 2912658. DOI: 10.1128/mBio.00018-10. View

Prabakaran M, He F, Meng T, Madhan S, Yunrui T, Jia Q . Neutralizing epitopes of influenza virus hemagglutinin: target for the development of a universal vaccine against H5N1 lineages. J Virol. 2010; 84(22):11822-30. PMC: 2977865. DOI: 10.1128/JVI.00891-10. View

Ninomiya A, Imai M, Tashiro M, Odagiri T . Inactivated influenza H5N1 whole-virus vaccine with aluminum adjuvant induces homologous and heterologous protective immunities against lethal challenge with highly pathogenic H5N1 avian influenza viruses in a mouse model. Vaccine. 2007; 25(18):3554-60. DOI: 10.1016/j.vaccine.2007.01.083. View

. Continuing progress towards a unified nomenclature for the highly pathogenic H5N1 avian influenza viruses: divergence of clade 2.2 viruses. Influenza Other Respir Viruses. 2009; 3(2):59-62. PMC: 4634523. DOI: 10.1111/j.1750-2659.2009.00078.x. View

10.

Yan J, Yoon H, Kumar S, Ramanathan M, Corbitt N, Kutzler M . Enhanced cellular immune responses elicited by an engineered HIV-1 subtype B consensus-based envelope DNA vaccine. Mol Ther. 2007; 15(2):411-21. DOI: 10.1038/sj.mt.6300036. View

11.

Gruber P, Gomersall C, Joynt G . Avian influenza (H5N1): implications for intensive care. Intensive Care Med. 2006; 32(6):823-9. PMC: 7095211. DOI: 10.1007/s00134-006-0148-z. View

12.

Baskin C, Bielefeldt-Ohmann H, Tumpey T, Sabourin P, Long J, Garcia-Sastre A . Early and sustained innate immune response defines pathology and death in nonhuman primates infected by highly pathogenic influenza virus. Proc Natl Acad Sci U S A. 2009; 106(9):3455-60. PMC: 2642661. DOI: 10.1073/pnas.0813234106. View

13.

Takano R, Nidom C, Kiso M, Muramoto Y, Yamada S, Sakai-Tagawa Y . Phylogenetic characterization of H5N1 avian influenza viruses isolated in Indonesia from 2003-2007. Virology. 2009; 390(1):13-21. PMC: 2861581. DOI: 10.1016/j.virol.2009.04.024. View

14.

Govorkova E, Webby R, Humberd J, Seiler J, Webster R . Immunization with reverse-genetics-produced H5N1 influenza vaccine protects ferrets against homologous and heterologous challenge. J Infect Dis. 2006; 194(2):159-67. DOI: 10.1086/505225. View

15.

Wrammert J, Koutsonanos D, Li G, Edupuganti S, Sui J, Morrissey M . Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. J Exp Med. 2011; 208(1):181-93. PMC: 3023136. DOI: 10.1084/jem.20101352. View

16.

Adams S, Sandrock C . Avian influenza: update. Med Princ Pract. 2010; 19(6):421-32. DOI: 10.1159/000320299. View

17.

Rimmelzwaan G, Kuiken T, van Amerongen G, Bestebroer T, Fouchier R, Osterhaus A . A primate model to study the pathogenesis of influenza A (H5N1) virus infection. Avian Dis. 2003; 47(3 Suppl):931-3. DOI: 10.1637/0005-2086-47.s3.931. View

18.

Hamouda T, Sutcliffe J, Ciotti S, Baker Jr J . Intranasal immunization of ferrets with commercial trivalent influenza vaccines formulated in a nanoemulsion-based adjuvant. Clin Vaccine Immunol. 2011; 18(7):1167-75. PMC: 3147313. DOI: 10.1128/CVI.00035-11. View

19.

Laddy D, Yan J, Khan A, Andersen H, Cohn A, Greenhouse J . Electroporation of synthetic DNA antigens offers protection in nonhuman primates challenged with highly pathogenic avian influenza virus. J Virol. 2009; 83(9):4624-30. PMC: 2668454. DOI: 10.1128/JVI.02335-08. View

20.

Chen M, Cheng T, Huang Y, Jan J, Ma S, Yu A . A consensus-hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses. Proc Natl Acad Sci U S A. 2008; 105(36):13538-43. PMC: 2533225. DOI: 10.1073/pnas.0806901105. View