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Conserved Internal Proteins as Potential Universal Vaccines

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Influenza Vaccines for the Future

Part of the book series: Birkhäuser Advances in Infectious Diseases ((BAID))

Abstract

In the current climate of an emerging pandemic (October 2009) and the need to vaccinate large populations in a short period of time, the traditional egg-based inactivated vaccine has been pushed, in terms of manufacturing capacity, to a remarkable degree. However, the enormity of the challenge to produce enough vaccine to cover areas beyond USA and Europe has led many investigators to look for a less cumbersome vaccine. Conserved antigens are clearly an attractive alternative as they offer the prospect of protection against a wider variety of influenza challenges.

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References

  1. Lamb RA, Lai CJ, Choppin PW (1981) Sequences of mRNAs derived from genome RNA segment 7 of influenza virus: colinear and interrupted mRNAs code for overlapping proteins. Proc Natl Acad Sci USA 78:4170–4174

    Article  PubMed  CAS  Google Scholar 

  2. Lamb RA, Choppin PW (1981) Identification of a second protein (M2) encoded by RNA segment 7 of influenza virus. Virology 112:729–737

    Article  PubMed  CAS  Google Scholar 

  3. Pinto LH, Holsinger LJ, Lamb RA (1992) Influenza virus M2 protein has ion channel activity. Cell 69:517–528

    Article  PubMed  CAS  Google Scholar 

  4. Zebedee SL, Lamb RA (1988) Influenza A virus M2 protein: monoclonal antibody restriction of virus growth and detection of M2 in virions. J Virol 62:2762–2772

    PubMed  CAS  Google Scholar 

  5. Treanor JJ, Tierney EL, Zebedee SL, Lamb RA, Murphy BR (1990) Passively transferred monoclonal antibody to the M2 protein inhibits influenza A virus replication in mice. J Virol 64:1375–1377

    PubMed  CAS  Google Scholar 

  6. Holsinger LJ, Lamb RA (1991) Influenza virus M2 integral membrane protein is a homotetramer stabilized by formation of disulfide bonds. Virology 183: 32–43

    Article  PubMed  CAS  Google Scholar 

  7. Feng J, Zhang M, Mozdzanowska K, Zharikova D, Hoff H, Wunner W, Couch RB, Gerhard W (2006) Influenza A virus infection engenders a poor antibody response against the ectodomain of matrix protein 2. Virol J 3:102

    Article  PubMed  Google Scholar 

  8. Neirynck S, Deroo T, Saelens X, Vanlandschoot P, Jou WM, Fiers W (1999) A universal influenza A vaccine based on the extracellular domain of the M2 protein. Nat Med 5:1157–1163

    Article  PubMed  CAS  Google Scholar 

  9. De Filette M, Martens W, Roose K, Deroo T, Vervalle F, Bentahir M, Vandekerckhove J, Fiers W, Saelens X (2008) An influenza A vaccine based on tetrameric ectodomain of matrix protein 2. J Biol Chem 283:11382–11387

    Article  PubMed  Google Scholar 

  10. Fan J, Liang X, Horton MS, Perry HC, Citron MP, Heidecker GJ, Fu TM, Joyce J, Przysiecki CT, Keller PM et al (2004) Preclinical study of influenza virus A M2 peptide conjugate vaccines in mice, ferrets, and rhesus monkeys. Vaccine 22:2993–3003

    Article  PubMed  CAS  Google Scholar 

  11. Fu TM, Grimm KM, Citron MP, Freed DC, Fan J, Keller PM, Shiver JW, Liang X, Joyce JG (2009) Comparative immunogenicity evaluations of influenza A virus M2 peptide as recombinant virus like particle or conjugate vaccines in mice and monkeys. Vaccine 27:1440–1447

    Article  PubMed  CAS  Google Scholar 

  12. Zebedee SL, Lamb RA (1989) Growth restriction of influenza A virus by M2 protein antibody is genetically linked to the M1 protein. Proc Natl Acad Sci U S A 86:1061–1065

    Article  PubMed  CAS  Google Scholar 

  13. Huleatt JW, Nakaar V, Desai P, Huang Y, Hewitt D, Jacobs A, Tang J, McDonald W, Song L, Evans RK et al (2008) Potent immunogenicity and efficacy of a universal influenza vaccine candidate comprising a recombinant fusion protein linking influenza M2e to the TLR5 ligand flagellin. Vaccine 26:201–214

    Article  PubMed  CAS  Google Scholar 

  14. Turley C, Taylor DN, Tussey L, Kavita U, Johnson C, Rupp RE, Wolfson J, Stanberry L, Shaw AR (2010) Safety and Immunogenicity of a recombinant M2e-flagellin influenza vaccine (STF2.4XM2e) in healthy adults

    Google Scholar 

  15. Talbot HK, Rock MT, Johnson C, Tussey L, Kavita U, Shanker A, Shaw AR, Taylor DN (2010) Immunopotentiation of trivalent influenza vaccine when given with VAX102, a recombinant influenza M2e vaccine fused to the TLR5 ligand flagellin. PLoS

    Google Scholar 

  16. Jegerlehner A, Schmitz N, Storni T, Bachmann MF (2004) Influenza A vaccine based on the extracellular domain of M2: weak protection mediated via antibody-dependent NK cell activity. J Immunol 172:5598–5605

    PubMed  CAS  Google Scholar 

  17. Bessa J, Schmitz N, Hinton HJ, Schwarz K, Jegerlehner A, Bachmann MF (2008) Efficient induction of mucosal and systemic immune responses by virus-like particles administered intranasally: implications for vaccine design. Eur J Immunol 38:114–126

    Article  PubMed  CAS  Google Scholar 

  18. Tam JP (1988) Synthetic peptide vaccine design: synthesis and properties of a high-density multiple antigenic peptide system. Proc Natl Acad Sci USA 85:5409–5413

    Article  PubMed  CAS  Google Scholar 

  19. Mozdzanowska K, Feng J, Eid M, Kragol G, Cudic M, Otvos L, Jr, Gerhard W (2003) Induction of influenza type A virus-specific resistance by immunization of mice with a synthetic multiple antigenic peptide vaccine that contains ectodomains of matrix protein 2. Vaccine 21:2616–2626

    Article  PubMed  CAS  Google Scholar 

  20. Zhao G, Sun S, Du L, Xiao W, Ru Z, Kou Z, Guo Y, Yu H, Jiang S, Lone Y et al (2009) An H5N1 M2e-based multiple antigenic peptide vaccine confers heterosubtypic protection from lethal infection with pandemic H1N1 virus. Virol J 7:151

    Google Scholar 

  21. Grandea AG, 3rd, Olsen OA, Cox TC, Renshaw M, Hammond PW, Chan-Hui PY, Mitcham JL, Cieplak W, Stewart SM, Grantham ML et al Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses. Proc Natl Acad Sci U S A

    Google Scholar 

  22. Fu TM, Freed DC, Horton MS, Fan J, Citron MP, Joyce JG, Garsky VM, Casimiro DR, Zhao Q, Shiver JW et al (2009) Characterizations of four monoclonal antibodies against M2 protein ectodomain of influenza A virus. Virology 385:218–226

    Article  PubMed  CAS  Google Scholar 

  23. Wang R, Song A, Levin J, Dennis D, Zhang NJ, Yoshida H, Koriazova L, Madura L, Shapiro L, Matsumoto A et al (2008) Therapeutic potential of a fully human monoclonal antibody against influenza A virus M2 protein. Antiviral Res 80:168–177

    Article  PubMed  CAS  Google Scholar 

  24. Garten W, Bosch FX, Linder D, Rott R, Klenk HD (1981) Proteolytic activation of the influenza virus hemagglutinin: The structure of the cleavage site and the enzymes involved in cleavage. Virology 115:361–374

    Article  PubMed  CAS  Google Scholar 

  25. Kawaoka Y, Webster RG (1988) Sequence requirements for cleavage activation of influenza virus hemagglutinin expressed in mammalian cells. Proc Natl Acad Sci USA 85:324–328

    Article  PubMed  CAS  Google Scholar 

  26. Bianchi E, Liang X, Ingallinella P, Finotto M, Chastain MA, Fan J, Fu TM, Song HC, Horton MS, Freed DC et al. (2005) Universal influenza B vaccine based on the maturational cleavage site of the hemagglutinin precursor. J Virol 79: 7380–7388

    Article  PubMed  CAS  Google Scholar 

  27. Sui J, Hwang WC, Perez S, Wei G, Aird D, Chen LM, Santelli E, Stec B, Cadwell G, Ali M et al (2009) Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol 16:265–273

    Article  PubMed  CAS  Google Scholar 

  28. Throsby M, van den Brink E, Jongeneelen M, Poon LL, Alard P, Cornelissen L, Bakker A, Cox F, van Deventer E, Guan Y et al (2008) Heterosubtypic neutralizing monoclonal antibodies cross-protective against H5N1 and H1N1 recovered from human IgM+ memory B cells. PLoS ONE 3:e3942

    Article  PubMed  Google Scholar 

  29. Ekiert DC, Bhabha G, Elsliger MA, Friesen RH, Jongeneelen M, Throsby M, Goudsmit J, Wilson IA (2009) Antibody recognition of a highly conserved influenza virus epitope. Science 324:246–251

    Article  PubMed  CAS  Google Scholar 

  30. Bommakanti G, Citron MP, Hepler RW, Callahan C, Heidecker GJ, Najar TA, Lu X, Joyce JG, Shiver JW, Casimiro DR et al Design of an HA2-based Escherichia coli expressed influenza immunogen that protects mice from pathogenic challenge. Proc Natl Acad Sci USA

    Google Scholar 

  31. Chen MW, Cheng TJ, Huang Y, Jan JT, Ma SH, Yu AL, Wong CH, Ho DD (2008) A consensus-hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses. Proc Natl Acad Sci USA 105:13538–13543

    Article  PubMed  CAS  Google Scholar 

  32. Donnelly JJ, Friedman A, Martinez D, Montgomery DL, Shiver JW, Motzel SL, Ulmer JB, Liu MA (1995) Preclinical efficacy of a prototype DNA vaccine: enhanced protection against antigenic drift in influenza virus. Nat Med 1:583–587

    Article  PubMed  CAS  Google Scholar 

  33. Epstein SL, Tumpey TM, Misplon JA, Lo CY, Cooper LA, Subbarao K, Renshaw M, Sambhara S, Katz JM (2002) DNA vaccine expressing conserved influenza virus proteins protective against H5N1 challenge infection in mice. Emerg Infect Dis 8:796–801

    Google Scholar 

  34. Hoelscher MA, Singh N, Garg S, Jayashankar L, Veguilla V, Pandey A, Matsuoka Y, Katz JM, Donis R, Mittal SK et al (2008) A broadly protective vaccine against globally dispersed clade 1 and clade 2 H5N1 influenza viruses. J Infect Dis 197:1185–1188

    Article  PubMed  Google Scholar 

  35. Rappuoli R, Del Giudice G, Nabel GJ, Osterhaus AD, Robinson R, Salisbury D, Stohr K, Treanor JJ (2009) Public health. Rethinking influenza. Science 326:50

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. VaxInnate, 3 Cedar Brook Drive, Suite # 1, Cranbury, NJ, 08512, USA

    Alan Shaw

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Correspondence to Alan Shaw .

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  1. Novartis Vaccines & Diagnostics S.r.l., Via Fiorentina 1, Siena, 53100, Italy

    Rino Rappuoli

  2. Novartis Vaccines & Diagnostics S.r.l., Via Fiorentina 1, Siena, 53100, Italy

    Giuseppe Del Giudice

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© 2011 Birkhäuser Basel

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Shaw, A. (2011). Conserved Internal Proteins as Potential Universal Vaccines. In: Rappuoli, R., Del Giudice, G. (eds) Influenza Vaccines for the Future. Birkhäuser Advances in Infectious Diseases. Springer, Basel. https://doi.org/10.1007/978-3-0346-0279-2_13

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