Influenza Vaccine Development

Graham, Barney

Abstract

Improvements in vaccines against influenza that increase breadth and duration of protection would improve worldwide ability to combat seasonal changes in influenza viruses (drift) and appearance of new pandemic strains (shift). This study aims to develop new platforms and vaccination strategies against influenza. Nanoparticles, DNA and adenoviral vectored vaccines have been developed against multiple seasonal and pandemic strains of influenza, including recently identified H1N1, H7N9, H5N1 avian flu and seasonal flu. In addition, studies are ongoing to identify and optimize vaccine antigens to present conserved regions of the influenza virus hemagglutinin (HA) in order to develop a vaccine that provides more universal protection. Testing has been conducted to evaluate candidates, as well as adjuvants to boost immune response, and determine the optimal strategies for immunization. Several candidates showed promising results and testing is continuing, using DNA and DNA prime with inactivated vaccine boost or nano particles displaying full length, stem, and/or receptor binding domain HA antigens.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIAAI005003-14
• Application #: 9161742
• Support Year: 14
• Fiscal Year: 2015

Institution

• Name: Niaid Extramural Activities

Publications

Erbelding, Emily J; Post, Diane J; Stemmy, Erik J et al. (2018) A Universal Influenza Vaccine: The Strategic Plan for the National Institute of Allergy and Infectious Diseases. J Infect Dis 218:347-354

Yassine, Hadi M; McTamney, Patrick M; Boyington, Jeffery C et al. (2018) Use of Hemagglutinin Stem Probes Demonstrate Prevalence of Broadly Reactive Group 1 Influenza Antibodies in Human Sera. Sci Rep 8:8628

Andrews, Sarah F; Graham, Barney S; Mascola, John R et al. (2018) Is It Possible to Develop a ""Universal"" Influenza Virus Vaccine? Immunogenetic Considerations Underlying B-Cell Biology in the Development of a Pan-Subtype Influenza A Vaccine Targeting the Hemagglutinin Stem. Cold Spring Harb Perspect Biol 10:

DeZure, Adam D; Coates, Emily E; Hu, Zonghui et al. (2017) An avian influenza H7 DNA priming vaccine is safe and immunogenic in a randomized phase I clinical trial. NPJ Vaccines 2:15

Andrews, Sarah F; Joyce, M Gordon; Chambers, Michael J et al. (2017) Preferential induction of cross-group influenza A hemagglutinin stem-specific memory B cells after H7N9 immunization in humans. Sci Immunol 2:

Wheatley, Adam K; Whittle, James R R; Lingwood, Daniel et al. (2015) H5N1 Vaccine-Elicited Memory B Cells Are Genetically Constrained by the IGHV Locus in the Recognition of a Neutralizing Epitope in the Hemagglutinin Stem. J Immunol 195:602-10

Yassine, Hadi M; Boyington, Jeffrey C; McTamney, Patrick M et al. (2015) Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection. Nat Med :

Whittle, James R R; Wheatley, Adam K; Wu, Lan et al. (2014) Flow cytometry reveals that H5N1 vaccination elicits cross-reactive stem-directed antibodies from multiple Ig heavy-chain lineages. J Virol 88:4047-57

Kanekiyo, Masaru; Wei, Chih-Jen; Yassine, Hadi M et al. (2013) Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies. Nature 499:102-6

Wei, Chih-Jen; Yassine, Hadi M; McTamney, Patrick M et al. (2012) Elicitation of broadly neutralizing influenza antibodies in animals with previous influenza exposure. Sci Transl Med 4:147ra114