2194. Natural H3N2 influenza A infection in humans expands memory B cells specific for the hemagglutinin stalk domain
Session: Poster Abstract Session: Host-Pathogen Interactions
Saturday, October 29, 2016
Room: Poster Hall
Background: The B cell response to influenza infection and vaccination is profoundly influenced by the composition of an individual’s memory B cell (MBC) pool. However, changes to the MBC pool induced by exposure to influenza in different forms are not well characterized.

 Methods: Here, we analyzed virus-specific B cell responses in 8 subjects infected with H3N2 influenza A virus (confirmed by PCR) during the 2012-13 season. Peripheral blood mononuclear cells and plasma were collected at the time of presentation with an influenza-like illness and on days 3, 10, and 28 thereafter.

Results: Hemagglutination inhibiting antibody titers against the prevalent H3N2 strain A/Victoria/361/2011 increased 2-4-fold in all subjects by day 28. Circulating IgG plasmablasts (PBs) specific for the Vic/11 H3 and the viral nucleoprotein commonly peaked on day 3. Approximately 25% of H3-specific IgG PBs bound the conserved stalk domain. IgA PBs included the same specificities, but numbers were low and variable. A wave of recently proliferated, non-antibody secreting B cells peaked on day 10. These included virus-specific cells and likely represented newly formed MBC precursors. In most subjects, H3 (head and stalk domain)- and nucleoprotein-specific IgG MBC frequencies progressively increased through day 10 and were maintained at day 28. Surprisingly, H1-specific IgG MBC frequencies also increased following H3N2 infection in a majority of subjects. Increases in virus-specific IgA MBC frequencies were smaller and variable.

Conclusion: Overall, we demonstrate that the specificities of MBC populations expanded by natural H3N2 infection reflect the early virus-specific PB response. Importantly, this includes IgG and IgA MBCs specific for the HA stalk domain, a target of broadly neutralizing antibodies that are poorly induced by inactivated H3N2 vaccination.

Brenda Tesini, MD1, Jessica Halliley, MS2, Ali Ellebedy, PhD3, Preshetha Kanagaiah, BS1, Christopher Anderson, MS1, Marta Dediego, PhD1, Jiong Wang, PhD1, Martin Zand, MD PhD1, Rafi Ahmed, PhD4, Florian Krammer, PhD5, John J. Treanor, MD6, David Topham, PhD1 and Mark Sangster, PhD1, (1)University of Rochester, Rochester, NY, (2)University of Rochester Medical Center, Rochester, NY, (3)Emory University, Atlanta, GA, (4)Emory University School of Medicine, Atlanta, GA, (5)Ichan School of Medicine at Mt. Sinai, New York, NY, (6)Medicine, University of Rochester Medical Center School of Medicine and Dentistry, Rochester, NY

Disclosures:

B. Tesini, None

J. Halliley, None

A. Ellebedy, None

P. Kanagaiah, None

C. Anderson, None

M. Dediego, None

J. Wang, None

M. Zand, None

R. Ahmed, None

F. Krammer, None

J. J. Treanor, None

D. Topham, None

M. Sangster, None

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