Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies

Masaru Kanekiyo, Chih-Jen Wei, Hadi M. Yassine, Patrick M. McTamney, Jeffrey C. Boyington, James R. R. Whittle, Srinivas S. Rao, Wing-Pui Kong, LingshuWang & Gary J. Nabel

Nature. (2013) 499, 102-106.

Speaker: Han Lee (李涵)                                                      Time: 13:00~14:00, Oct. 23, 2013

Commentator: Dr. Bei-Chang Yang (楊倍昌 老師)            Place: Room 601

Abstract

The influenza virus has caused several epidemics worldwide and led to one billion cases of infection annually, and around 250,000 to 500,000 deaths to date (1). Influenza viruses mutate constantly, and therefore the components of influenza vaccines are reviewed and updated frequently to ensure effectiveness of the vaccines (2). However, the majority of the world’s production capacity of influenza vaccine is concentrated in several large multinational manufacturers. Safe and effective vaccines are more urgently needed in the otherwise developing countries. In this study,the authors proposed a new strategy for influenza vccine. They designed self-assembling nanoparticles that elicit more broader and potent immunity than traditional influenza vaccines. The viralhaemagglutinin (HA) was genetically fused to ferritin, a ubiquitous intracellular protein of 24 identical polypeptides that stores and releases iron. The HA was inserted on the interface of adjacent ferritins so that it spontaneously assembled and generated eight trimeric viral spikes on its surface. Murine and ferrets immunized with this influenza nanoparticle vaccine elicited haemagglutinationinhibition antibody titers which were ten-fold higher than those from the licensed inactivated vaccines. Furthermore, neutralizing antibodies produced antagonize two highly conserved vulnerable HA structures, the stem and the receptor binding site on the head, which are targets of universal vaccines (3). Antibodies generated by a 1999 HA-nanoparticle vaccine neutralized H1N1 viruses from 1934 to 2007 and protected ferrets from an unmatched 2007 H1N1 virus challenge. This structure-based, self-assembling synthetic nanoparticle vaccine improves the potency and breadth of influenza virus immunity. HA-nanoparticle technology therefore represents a foundation for a new generation of influenza vaccines and could be adapted to create analogous vaccines for a wide variety of pathogens.

References

1. Salomon, R., and R. G. Webster. (2009) The influenza virus enigma. Cell. 136, 402-410.
2. Linda C. Lambert, P. D., and Anthony S. Fauci, M.D. (2010) Influenza Vaccines for the Future. N Engl J Med. 363, 2036-2044.
3. Sui, J., W. C. Hwang, S. Perez, G. Wei, D. Aird, L. M. Chen, E. Santelli, B. Stec, G. Cadwell, M. Ali, H. Wan, A. Murakami, A. Yammanuru, T. Han, N. J. Cox, L. A. Bankston, R. O. Donis, R. C. Liddington, and W. A. Marasco. (2009) Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol. 16, 265-273.