Influenza Virus Hemagglutinin Stalk-based Antibodies and Vaccines

Overview

Journal Curr Opin Virol

Publisher Elsevier

Specialty Microbiology

Date 2013 Aug 28

PMID 23978327

Citations 208

Authors

Florian Krammer

Peter Palese

Affiliations

Soon will be listed here.

Abstract

Antibodies against the conserved stalk domain of the hemagglutinin are currently being discussed as promising therapeutic tools against influenza virus infections. Because of the conservation of the stalk domain these antibodies are able to broadly neutralize a wide spectrum of influenza virus strains and subtypes. Broadly protective vaccine candidates based on the epitopes of these antibodies, for example, chimeric and headless hemagglutinin structures, are currently under development and show promising results in animals models. These candidates could be developed into universal influenza virus vaccines that protect from infection with drifted seasonal as well as novel pandemic influenza virus strains therefore obviating the need for annual vaccination, and enhancing our pandemic preparedness.

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References

Miller M, Gardner T, Krammer F, Aguado L, Tortorella D, Basler C . Neutralizing antibodies against previously encountered influenza virus strains increase over time: a longitudinal analysis. Sci Transl Med. 2013; 5(198):198ra107. PMC: 4091683. DOI: 10.1126/scitranslmed.3006637. View

Tan G, Krammer F, Eggink D, Kongchanagul A, Moran T, Palese P . A pan-H1 anti-hemagglutinin monoclonal antibody with potent broad-spectrum efficacy in vivo. J Virol. 2012; 86(11):6179-88. PMC: 3372189. DOI: 10.1128/JVI.00469-12. View

Throsby M, van den Brink E, Jongeneelen M, Poon L, Alard P, Cornelissen L . Heterosubtypic neutralizing monoclonal antibodies cross-protective against H5N1 and H1N1 recovered from human IgM+ memory B cells. PLoS One. 2008; 3(12):e3942. PMC: 2596486. DOI: 10.1371/journal.pone.0003942. View

Gerdil C . The annual production cycle for influenza vaccine. Vaccine. 2003; 21(16):1776-9. DOI: 10.1016/s0264-410x(03)00071-9. View

Sui J, Hwang W, Perez S, Wei G, Aird D, Chen L . Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol. 2009; 16(3):265-73. PMC: 2692245. DOI: 10.1038/nsmb.1566. View

Sangster M, Baer J, Santiago F, Fitzgerald T, Ilyushina N, Sundararajan A . B cell response and hemagglutinin stalk-reactive antibody production in different age cohorts following 2009 H1N1 influenza virus vaccination. Clin Vaccine Immunol. 2013; 20(6):867-76. PMC: 3675965. DOI: 10.1128/CVI.00735-12. View

Wei C, Boyington J, McTamney P, Kong W, Pearce M, Xu L . Induction of broadly neutralizing H1N1 influenza antibodies by vaccination. Science. 2010; 329(5995):1060-4. DOI: 10.1126/science.1192517. View

Krammer F, Margine I, Tan G, Pica N, Krause J, Palese P . A carboxy-terminal trimerization domain stabilizes conformational epitopes on the stalk domain of soluble recombinant hemagglutinin substrates. PLoS One. 2012; 7(8):e43603. PMC: 3426533. DOI: 10.1371/journal.pone.0043603. View

Dreyfus C, Ekiert D, Wilson I . Structure of a classical broadly neutralizing stem antibody in complex with a pandemic H2 influenza virus hemagglutinin. J Virol. 2013; 87(12):7149-54. PMC: 3676097. DOI: 10.1128/JVI.02975-12. View

10.

Hu Y, Lu S, Song Z, Wang W, Hao P, Li J . Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance. Lancet. 2013; 381(9885):2273-9. DOI: 10.1016/S0140-6736(13)61125-3. View

11.

Kanekiyo M, Wei C, Yassine H, McTamney P, Boyington J, Whittle J . Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies. Nature. 2013; 499(7456):102-6. PMC: 8312026. DOI: 10.1038/nature12202. View

12.

Schneemann A, Speir J, Tan G, Khayat R, Ekiert D, Matsuoka Y . A virus-like particle that elicits cross-reactive antibodies to the conserved stem of influenza virus hemagglutinin. J Virol. 2012; 86(21):11686-97. PMC: 3486276. DOI: 10.1128/JVI.01694-12. View

13.

Iioka F, Sada R, Maesako Y, Nakamura F, Ohno H . Outbreak of pandemic 2009 influenza A/H1N1 infection in the hematology ward: fatal clinical outcome of hematopoietic stem cell transplant recipients and emergence of the H275Y neuraminidase mutation. Int J Hematol. 2012; 96(3):364-9. PMC: 7101624. DOI: 10.1007/s12185-012-1139-1. View

14.

de Jong J, Beyer W, Palache A, Rimmelzwaan G, Osterhaus A . Mismatch between the 1997/1998 influenza vaccine and the major epidemic A(H3N2) virus strain as the cause of an inadequate vaccine-induced antibody response to this strain in the elderly. J Med Virol. 2000; 61(1):94-9. View

15.

Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W . Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med. 2013; 368(20):1888-97. DOI: 10.1056/NEJMoa1304459. View

16.

Friesen R, Koudstaal W, Koldijk M, Weverling G, Brakenhoff J, Lenting P . New class of monoclonal antibodies against severe influenza: prophylactic and therapeutic efficacy in ferrets. PLoS One. 2010; 5(2):e9106. PMC: 2817000. DOI: 10.1371/journal.pone.0009106. View

17.

Jegaskanda S, Job E, Kramski M, Laurie K, Isitman G, De Rose R . Cross-reactive influenza-specific antibody-dependent cellular cytotoxicity antibodies in the absence of neutralizing antibodies. J Immunol. 2013; 190(4):1837-48. DOI: 10.4049/jimmunol.1201574. View

18.

DeVries A, Wotton J, Lees C, Boxrud D, Uyeki T, Lynfield R . Neuraminidase H275Y and hemagglutinin D222G mutations in a fatal case of 2009 pandemic influenza A (H1N1) virus infection. Influenza Other Respir Viruses. 2012; 6(6):e85-8. PMC: 4941703. DOI: 10.1111/j.1750-2659.2011.00329.x. View

19.

Wrammert J, Smith K, Miller J, Langley W, Kokko K, Larsen C . Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature. 2008; 453(7195):667-71. PMC: 2515609. DOI: 10.1038/nature06890. View

20.

Ohmit S, Petrie J, Cross R, Johnson E, Monto A . Influenza hemagglutination-inhibition antibody titer as a correlate of vaccine-induced protection. J Infect Dis. 2011; 204(12):1879-85. DOI: 10.1093/infdis/jir661. View