Confronting the avian influenza threat: vaccine development for a potential pandemic

Iain Stephenson, Karl G Nicholson, John M Wood, Maria C Zambon, Jacqueline M Katz, Iain Stephenson, Karl G Nicholson, John M Wood, Maria C Zambon, Jacqueline M Katz

Abstract

Sporadic human infection with avian influenza viruses has raised concern that reassortment between human and avian subtypes could generate viruses of pandemic potential. Vaccination is the principal means to combat the impact of influenza. During an influenza pandemic the immune status of the population would differ from that which exists during interpandemic periods. An emerging pandemic virus will create a surge in worldwide vaccine demand and new approaches in immunisation strategies may be needed to ensure optimum protection of unprimed individuals when vaccine antigen may be limited. The manufacture of vaccines from pathogenic avian influenza viruses by traditional methods is not feasible for safety reasons as well as technical issues. Strategies adopted to overcome these issues include the use of reverse genetic systems to generate reassortant strains, the use of baculovirus-expressed haemagglutinin or related non-pathogenic avian influenza strains, and the use of adjuvants to enhance immunogenicity. In clinical trials, conventional surface-antigen influenza virus vaccines produced from avian viruses have proved poorly immunogenic in immunologically naive populations. Adjuvanted or whole-virus preparations may improve immunogenicity and allow sparing of antigen.

Figures

Figure 1
Figure 1
Returning from a shopping trip in Hanoi, Vietnam (photo JM Katz).
Figure 2
Figure 2
The effect of highly pathogenic H5N1 virus on ducklings in Vietnam (photo T Tumpey).
Figure 3
Figure 3
Effect of alum-adjuvant on immunogenicity of monovalent influenza A/Singapore/1/57 (H2N2) in immunologically naive people aged 18–30 years (data from reference 71). Vaccine administered on day 0 and day 21. GMT=geometric mean titre. Al=aluminum mineral adjuvant.
Figure 4
Figure 4
Geometric mean titres of antibody for MF59-adjuvanted and conventional surface-antigen H5N3 vaccine before and after two and thre doses of vaccine (data from , A=Haemagglutination-inhibition (H5N3); B=Microneutralisation (H5N3); C=Single radial haemolysis (H5N3); D=single radial haemolysis (H5N1)

References

    1. Potter CW. Chronicle of influenza pandemics. In: Nicholson KG, Webster RG, Hay AJ, editors. The textbook of influenza. Blackwell; Oxford: 1998. pp. 3–18.
    1. WHO disease alert. 2004. Confirmed human cases of avian influenza H5N1. (accessed June 30, 2004).
    1. Hien TT, Liem NT, Dung NT. Avian influenza (H5N1) in 10 patients in Vietnam. N Engl J Med. 2004;350:1179–1188.
    1. Ruigrok RWH. Structure of influenza A, B and C. In: Nicholson KG, Webster RG, Hay AJ, editors. The textbook of influenza. Blackwell Science; Oxford: 1998. pp. 29–42.
    1. Webster RG, Bean WJ, Gorman OT, Chambers TM, Kawaoka Y. Evolution and ecology of influenza A viruses. Microbiol Rev. 1992;56:152–179.
    1. Rohm C, Zhou NA, Suss JC, Mackenzie J, Webster RG. Characterisation of a novel influenza haemagglutinin H15: criteria for determination of influenza A subtypes. Virology. 1996;218:253–257.
    1. Rogers GN, Paulson JC, Daniels RS, Skehel JJ, Wilson IA, Wiley DC. Single amino acid substitutions in influenza haemagglutinin change receptor binding specificity. Nature. 1983;304:76–78.
    1. Connor RJ, Kawaoka Y, Webster RG, Paulson JC. Receptor specificity in human, avian and equine H2 and H3 influenza virus isolates. Virology. 1994;205:17–23.
    1. Ito T, Suzuki Y, Mitnaul L, Vines A, Kida H, Kawaoka Y. Receptor specificity of influenza A viruses correlate with agglutination of erythrocytes from different animal species. Virology. 1997;227:492–499.
    1. Matrosovich M, Tuzikov A, Bovin N. Early alterations of the receptor binding properties of the H1, H2 and H3 avian influenza virus haeamgglutinins after their introduction into mammals. J Virol. 2000;74:8502–8512.
    1. Kawaoka Y, Krauss S, Webster RG. Avian to human transmission of the PB1 gene of influenza A virus in the 1957 and 1968 pandemic. J Virol. 1989;63:4603–4608.
    1. Scholtisrek C, Hinshow VS, Olsen CW. Influenza in pigs and their role as the intermediate host. In: Nicholson KG, Webster RG, Hay AJ, editors. The textbook of influenza. Blackwell; Oxford: 1998. pp. 137–144.
    1. Matrosovich M, Zhou N, Kawaoka Y, Webster RG. The surface glycoproteins of H5 influenza viruses isolated from humans, chickens and wild aquatic birds have distinguishable properties. J Virol. 1999;73:1146–1155.
    1. Li KS, Xu KM, Peiris JSM. Characterisation of H9 subtype influenza viruses from the ducks of southern china: a candidate for the next influenza pandemic in humans? J Virol. 2003;77:6988–6994.
    1. Shortridge KF, Stuart-Harris CH. An influenza epicenter? Lancet. 1982;2:812–813.
    1. Beare AS, Webster RG. Replication of avian influenza viruses in humans. Arch Virol. 1991;119:37–42.
    1. Kurtz J, Manvell RJ, Banks J. Avian influenza isolated from a woman with conjunctivitis. Lancet. 1996;348:901–902.
    1. Claas ECJ, Osterhaus ADME, van Beek R. Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet. 1998;351:472–477.
    1. Yuen KY, Chan PKS, Peiris MK. Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet. 1998;351:467–471.
    1. Katz JM, Lim W, Buxton-Bridges C. Antibody responses in individuals infected with avian influenza A (H5N1) viruses and detection of anti-H5 antibody among household and social contacts. J Infect Dis. 1999;180:1763–1770.
    1. Bender C, Hall H, Huang J. Characterization of the surface proteins of influenza A H5N1 viruses isolated from humans in 1997–1998. Virology. 1999;254:115–123.
    1. Peiris JSM, Yuen KY, Leung CW. Human infection with influenza H9N2. Lancet. 1999;354:916–917.
    1. Uyeki TM, Chong YH, Katz JM. Lack of evidence for human-to-human transmission of avian influenza A (H9N2) viruses in Hong Kong, China 1999. Emerg Infect Dis. 2002;8:154–159.
    1. Peiris JSM, Yu WC, Leung CW. Re-emergence of fatal human influenza A subtype H5N1 disease. Lancet. 2004;363:617–619.
    1. Edwards L, Nguyen D, Lu X, et al. Antigenic characterization of recent avian influenza A H5N1 viruses isolated from humans. International Congress Series 2004; in press.
    1. Fouchier RA, Schneeberger, Rozendall FW. Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory respiratory distress syndrome. Proc Nat Acad Sci USA. 2004;101:1356–1361.
    1. Koopmans M, Wilbrink B, Conyn M. Transmission of H7N7 avian influenza A virus to human beings during a large outbreak in commercial poultry farms in the Netherlands. Lancet. 2004;363:587–593.
    1. WHO disease alert: 10 December 2003. Influenza A (H9N2) in Hong Kong Special Administrative Region of China. (accessed July 5, 2004)
    1. WHO disease alert, 22 January 2004 Avian influenza H5N1 infection in humans: urgent need to eliminate the animal reservoir-update 5. (accessed July 5, 2004)
    1. Chotpirayasunondh T, Lochindarat S, Srisan P. Cases of influenza A (H5N1)-Thailand 2004. MMWR Morb Mortal Wkly Rep. 2004;53:101–103.
    1. Avian influenza virus A (H10N7) circulating among humans in Egypt. Archive number: 20040524.1392.
    1. Sims LD, Guan Y, Ellis TM. An update on avian influenza in Hong Kong in 2002. Avian Dis. 2003;47:1083–1086.
    1. Guan Y, Peiris M, Kong KF. H5N1 influenza viruses isolated from geese in Southeastern China: evidence for genetic reassortment and interspecies transmission to ducks. Virology. 2002;292:16–23.
    1. Guo YJ, Li J, Cheng X, Wang M, Zhou Y. Discovery of man infected by avian influenza virus. Chin J Exp Clin Virol. 1999;13:105–108.
    1. Eick A, Hu-Primmer J, Rowe T, Masseoud F, Fukuda K, Lim W. Seroprevalence of antibody to H9N2 viruses in poultry workers of Hong Kong. Poster 52. International Conference on Emerging Infectious Disease 2000; July 2000; Atlanta, GA, USA.
    1. Guan Y, Shortridge KF, Krauss S, Webster RG. Molecular characterization of H9N2 influenza viruses: were they the donors of the internal genes of H5N1 viruses in Hong Kong. Proc Natl Acad Sci USA. 1999;96:9363–9367.
    1. Lin YP, Shaw M, Gregory V, Cameron K, Lim W, Klimov A. Influenza A viruses: relationship between H9N2 relationship between H9N2 and H5N1 human isolates. Proc Nat Acad Sci USA. 2000;97:9654–9658.
    1. Alexander DJ. Ecology of avian influenza in domestic birds. In: Dodet B, Vicari M, editors. Emergence and control of zoonotic ortho- and paramyxovirus diseases. John Libbey Eurotext; Paris: 2001. pp. p25–p33.
    1. Peiris JSM, Guan Y, Ghose P. Cocirculation of avian H9N2 and human H3N2 viruses in pigs in southern China. In: Osterhaus ADME, Cox NJ, Hampson A, editors. Proceedings of options for the control of influenza IV. Excerpta Medica; Amsterdam: 2001. pp. 195–200.
    1. Ninomiya A, Takda A, Okazaki K, Shortridge K, Kida H. Seropidemiological evidence of avian H4, H5 and H9 influenza viruses transmission to pigs in south eastern China. Vet Microbio. 2002;88:107–114.
    1. Saito T, Lim W, Suzuki T. Characterisation of a human H9N2 influenza virus isolated in Hong Kong. Vaccine. 2002;20:125–133.
    1. Chin PS, Hoffmann E, Webby RJ. Molecular evolution of H6 influenza viruses from poultry in south eastern China: prevalence of H6N1 influenza viruses possessing seven A/HongKong/156/97 H5N1- like genes in poultry. J Virol. 2002;76:507–516.
    1. Makarova NV, Kaverin NV, Krauss S, Senne D, Webster RG. Transmission of Eurasian avian H2 influenza virus to shorebirds in North America. J Gen Virol. 1999;80:3167–3171.
    1. Lazarowitz SG, Choppin PW. Enhancement of the infectivity of influenza A and B viruses by proteolytic cleavage of the haemagglutinin polypeptide. Virology. 1975;68:440–454.
    1. Bosch FX, Orlich M, Klenk HD, Rott R. Proteolytic cleavage of influenza virus haemagglutinins: primary structure of the connecting peptide between HA1 and HA2 determines proteolytic cleavability and pathogenicity of avian influenza viruses. Virology. 1981;113:725–735.
    1. Garcia-Sastre A. Inhibition of interferon-mediated antiviral responses by influenza A viruses and other negative-strand RNA viruses. Virology. 2001;279:375–384.
    1. Goto H, Kawaoka Y. A novel mechanism for the acquisition of virulence by a human influenza A virus. Proc Nat Acad Sci USA. 1998;95:10224–10228.
    1. Lu X, Tumpey TM, Morken T, Zaki SR, Cox NJ, Katz JM. A mouse model for the evaluation of pathogenesis and immunity to influenza A (H5N1) viruses isolated from humans. J Virol. 1999;73:5903–5911.
    1. Katz J, Lu X, Tumpey T, Smith C, Shaw M, Subbarao K. Molecular correlates of influenza A H5N1 virus pathogenesis. J Virol. 2000;74:10807–10810.
    1. Gao P, Watanabe S, Ito T. Biological heterogeneity, including systemic replication in mice, of H5N1 influenza A virus isolates from humans in Hong Kong. J Virol. 1999;73:3184–3189.
    1. Zitzow LA, Rowe T, Morken T. Pathogenesis of avian influenza A H5N1 viruses in ferrets. J Virol. 2002;76:4420–4429.
    1. Hatta M, Gao P, Halfman P, Kawaoka Y. Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science. 2001;293:1840–1842.
    1. Lu X, Cho D, Hall H. Pathogenicity and antigenicity of a new influenza A (H5N1) virus isolated from duck meat. J Med Virol. 2003;69:553–559.
    1. Cheung CY, Poon LLM, Lau AS. Induction of proinflammatory cytokines in human macrophages by influenza A H5N1 viruses: a mechanism for the unusual severity of human disease? Lancet. 2002;360:1831–1837.
    1. Seo SH, Hoffmann E, Webster RG. Lethal H5N1 influenza viruses escape host anti-viral cytokine responses. Nat Med. 2002;8:950–954.
    1. Reid AR, Fanning TG, Hultin JV, Taubenberger JK. Origin and evolution of the 1918 Spanish influenza virus heamagglutinin gene. Proc Nat Acad Sci USA. 1999;96:1651–1656.
    1. Reid AR, Fanning TG, Janczewski TA, Taubenberger JK. Characterisation of the 1918 Spanish influenza virus neuraminidase gene. Proc Nat Acad Sci USA. 2000;97:6785–6790.
    1. Furminger IGS. Vaccine production. In: Nicholson KG, Webster RG, Hay AJ, editors. The textbook of influenza. Blackwell; Oxford: 1998. pp. 325–332.
    1. Meiklejohn G, Eickhoff TC, Graves P. Antigenic drift and efficacy of influenza virus vaccines. J Infect Dis. 1978;138:618–624.
    1. Nichol KL. Efficacy/clinical effectiveness of inactivated influenza virus vaccines in adults. In: Nicholson KG, Webster RG, Hay AJ, editors. The textbook of influenza. Blackwell; Oxford: 1998. pp. 358–372.
    1. Potter CW, Oxford JS. Determinants of immunity to influenza infection in man. Br Med Bull. 1979;35:69–75.
    1. Delem A, Jovanovic D. Correlation between rate of infection and pre-existing titer of serum antibody as determined by single radial haemolysis during an epidemic of influenza A/Victoria/3/75. J Infect Dis. 1978;137:194–199.
    1. Circulaire no 96–0661: 1–22. Committee for proprietary medicinal products; London: September 1996. Note for guidance on harmonisation of requirements for influenza vaccines, CPMP/BWP/214/96.
    1. Kistner O, Barrett PN, Mundt W. Development of a Vero cell-derived influenza whole virus vaccine. Dev Biol Stand. 1999;98:101–110.
    1. Medical Research Council Antibody responses and reactogenicity of graded doses of inactivated influenza A/New Jersey.76 whole virus vaccine in humans. J Infect Dis. 1977;136:S475–S483.
    1. Parkman PD, Hopps HE, Rastogi SC. Summary of influenza virus vaccine trials in adults. J Infect Dis. 1977;136:S722–S730.
    1. Wright PF, Thompson J, Vaughan WK. Trials of influenza A/New Jersey/76 virus vaccine in normal children: an overview of age related antigenicity and reactogenicity. J Infect Dis. 1977;136:S731–S741.
    1. Nicholson KG, Tyrrell DA, Harrison P. Clinical studies of monovalent inactivated whole virus and subunit A/USSR/77 (H1N1) vaccine: serological responses and clinical reactions. J Biol Stand. 1979;7:123–136.
    1. Jennings R, Potter CW, Massey PMO. Responses of volunteers to inactivated influenza virus vaccines. J Hyg. 1981;86:1–16.
    1. Davenport FM, Henessey AV, Askin FB. Lack of adjuvant effect of AlPO4 on purified influenza virus haemagglutinin in man. J Immunol. 1968;100:1139–1140.
    1. Hehme N, Engelmann H, Kunzel W. Pandemic preparedness: lessons learnt from H2N2 and H9N2 candidate vaccines. Med Microbiol Immunol. 2002;191:203–208.
    1. Takada A, Kuboki N, Okazaki K. Avirulent avian influenza virus as a vaccine strain against a potential human pandemic. J Virol. 1999;73:8303–8307.
    1. Wood JM, Major D, Daly J. Vaccine against H5N1 influenza. Vaccine. 2000;18:579–580.
    1. Rimmelzwann GF, Class EJ, van Amerongen G, de Jong JC, Osterhaus ADME. ISCOM vaccine induced protection against a lethal challenge with a human H5N1 influenza virus. Vaccine. 1999;17:1355–1358.
    1. Nicholson KG, Colegate AC, Podda A. Safety and antigenicity of nonadjuvanted and MF59- adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a randomised trial of two potential vaccines against H5N1 influenza. Lancet. 2001;357:1937–1943.
    1. Stephenson I, Nicholson KG, Colegate A. Boosting immunity to influenza H5N1 with MF59- adjuvanted H5N3 A/Duck/Singapore/97 vaccine in a primed human population. Vaccine. 2003;21:1687–1693.
    1. Leese J, Tamblyn SE. Pandemic planning. In: Nicholson KG, Webster RG, Hay AJ, editors. The textbook of influenza. Blackwell; Oxford: 1998. pp. 53–58.
    1. Profeta ML, Palladino G. Serological evidence of human infections with avian influenza viruses. Arch Virol. 1986;90:355–360.
    1. Rowe T, Abernathy RA, Primmer JH. Detection of antibody to avian influenza (H5N1) virus in human sera by using a combination of serological assays. J Clin Micro. 1999;37:937–943.
    1. Stephenson I, Zambon MC, Wood JM, Nicholson KG. Sialic acid receptor specificity of erythrocytes affects haemagglutinin-inhibition test detection of antibody to avian haemagglutinin. J Med Virol. 2003;70:391–398.
    1. Wood JM, Melzack D, Newman RW. A single radial haemolysis assay for antibody to H5 haemagglutinin. In: Osterhaus ADME, Cox NJ, Hampson A, editors. Proceedings of options for the control of influenza IV. Excerpta Medica; Amsterdam: 2001. pp. 461–466.
    1. Stephenson I, Wood JM, Nicholson KG, Zambon MC, Charlett A. Detection of anti-H5 responses in human sera by HI using horse erythrocytes following MF59-adjuvanted influenza A/Duck/Singapore/97 vaccine. Virus Research. 2004;103:91–95.
    1. Laky DL, Treanor JJ, Betts RF. Recombinant baculovirus influenza A haemagglutinin vaccines are well tolerated and immunogenic in healthy adults. J Infect Dis. 1996;174:838–841.
    1. Treanor JJ, Betts RF, Smith GE. Evaluation of recombinant haemagglutinin expressed in insect cells as an influenza vaccine in young and elderly adults. J InfectDis. 1996;173:1467–1470.
    1. Crawford J, Wilkinson B, Vosnesensky A. Baculovirus-derived haemagglutinin vaccines protect against lethal infection by avian H7 and H5 subtypes. Vaccine. 1999;17:2265–2274.
    1. Treanor JJ, Wilkinson BE, Masseoud M. Safety and immunogenicity of a recombinant hemagglutinin vaccine for H5 influenza in humans. Vaccine. 2001;19:1732–1737.
    1. Liu M, Wood JM, Ellis T. Preparation of a standardized, efficacious agricultural H5N3 vaccine by reverse genetics. Virology. 2003;314:580–590.
    1. Subbarao K, Chen H, Swayne D. Evaluation of a genetically modified reassortant H5N1 influenza A virus vaccine candidate generated by plasmid-based reverse genetics. Virology. 2003;305:192–200.
    1. Sonoguchi T, Naito H, Hara M, Takeuchi Y, Fukumi H. Cross-subtype protection in humans during sequential overlapping and/or concurrent epidemics caused by H3N2 and H1N1 influenza viruses. J Infect Dis. 1985;151:81–88.
    1. Ulmer J. Influenza DNA vaccines. Vaccine. 2002;20:S74–S76.
    1. Kodihalli S, Kobasa DL, Webster RG. Strategies for inducing protection against avian influenza A virus subtypes with DNA vaccines. Vaccine. 2000;18:2592–2599.
    1. Bright RA, Ross TM, Subbarao K, Robinson HL, Katz JM. Impact of glycosylation on the immunogenicity of a DNA based influenza H5 vaccine. Virology. 2003;308:270–278.
    1. Epstein SL, Tumpey T, Misplon JA. DNA vaccine expressing conserved influenza virus proteins protective against H5N1 challenge infection in mice. Emerg Infect Dis. 2002;8:796–801.
    1. Sambhara S, Kurichh A, Miranda R. Heterotypic immunity against human influenza A viruses including recently emerged avian H5 and H9 viruses induced by ISCOM vaccine in mice requires both cytotoxic T-lymphocyte and macrophage function. Cell Immunol. 2001;211:143–153.
    1. Rimmelzwaan GF, Nieuwkoop N, Brandenburg A. A randomized, double blind study in young healthy adults comparing cell mediated and humoral immune responses induced by influenza ISCOM vaccines and conventional vaccines. Vaccine. 2000;191:180–187.
    1. Tumpey T, Renshaw M, Clements JD, Katz JM. Mucosal delivery of inactivated influenza vaccine induces B cell dependent heterosubtypic crossprotection against lethal influenza A H5N1 virus infection. J Virol. 2001;75:5141–5150.
    1. Lu X, Renshaw M, Tumpey T, Kelly G, Hu-Primmer J, Katz J. Immunity to influenza A H9N2 viruses induced by infection and vaccination. J Virol. 2001;75:4896–4901.
    1. Chen H, Subbarao K, Swayne D. Generation and evaluation of a high-growth reassortant H9N2 influenza A virus as a pandemic vaccine candidate. Vaccine. 2003;21:1974–1979.
    1. Stephenson I, Nicholson KG, Gluck R. Safety and antigenicity of whole virus and subunit influenza A/Hong Kong/1073/99 (H9N2) vaccine in healthy adults: phase I randomised trial. Lancet. 2003;13:1959–1966.
    1. Beyer WEP, Palache AM, de Jong JC, Osterhaus ADME. Cold-adapted live influenza vaccine versus inactivated vaccine: systemic vaccine reactions, local and systemic antibody responses and vaccine efficacy: a meta-analysis. Vaccine. 2002;20:1340–1353.
    1. Cha T, Kao K, Zhao J. Genotypic stability of coldadapted influenza vaccine in an efficacy clinical trial. J Clin Microbiol. 2000;38:839–845.
    1. Li S, Liu C, Klimov A. Recombinant influenza A virus vaccines for the pathogenic human A/Hong Kong/97 (H5N1) viruses. J Infect Dis. 1999;179:1132–1138.
    1. Cox RJ, Brokstad, Ogra P. Influenza virus: immunity and vaccination strategies. Comparison of the immune response to inactivated and live, attenuated influenza vaccines. Scand J Immunol. 2004;59:1–15.
    1. Belshe RB, Mendelman PM, Treanor JJ. The efficacy of live attenuated cold adapted trivalent intranasal influenza virus vaccine in children. N Eng J Med. 1998;338:1405–1412.
    1. Takada A, Matsushita S, Ninomiya A. Intranasal immunization with formalin-inactivated virus vaccine induces a broad spectrum of heterosubtypic immunity against influenza A virus infection in mice. Vaccine. 2003;21:3212–3218.
    1. Stephenson I, Nicholson KG. Influenza: vaccination and treatment. Eur Resp J. 2001;17:1–12.

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