838. Lifelong persistence of circulating human B cells specifying monoclonal antibodies to pandemic 1957 H2N2 influenza virus that target the receptor-binding domain
Session: Oral Abstract Session: Innate and Adaptive Immunity to Infections
Saturday, October 22, 2011: 8:45 AM
Room: 156ABC
Background: We had previously generated human monoclonal antibodies against the 1918 H1N1 influenza A virus from survivors of the pandemic, but it was not clear whether B cells specifying monoclonal antibodies to the 1957 or 1968 pandemic virus were still present in the peripheral blood of human donors. Investigation of the human antibody response to the 1957 pandemic H2N2 influenza A virus has been limited to serology, and there is little data on the human B cell response to either virus at the molecular level.

Methods: We generated three human monoclonal antibodies (mAbs) to the pandemic H2N2 virus and two mAbs against the pandemic H3N2 virus from the peripheral blood of healthy donors who were born between 1950 and 1968 using hybridoma technology. Each of the five antibodies was tested in hemagglutination activation inhibition (HAI) assays against a panel of representative H1, H2, H3, or H5 viruses. Antibody escape mutant viruses were selected by incubating 1957 H2N2 virus or 1968 H3N2 virus with neutralizing antibody followed by inoculation of the mixture in embryonated chicken eggs.

Results: Each of the five mAbs exhibited HAI activity and thus recognized the hemagglutinin (HA) globular head domain. None of the H2-specific antibodies inhibited H3 virus (and vice versa). H2N2-specific mAb 8F8 elicited mutations in positions 137 and 193, mAb 8M2 in position 135 of HA all immediately adjacent to the receptor-binding domain (RBD). 

Conclusion: These subjects possessed B cells encoding potent neutralizing antibodies specific for a highly conserved region in the HA of the pandemic H2N2 virus in their peripheral blood for at least 43 years after circulation of the virus. These studies suggest a high preponderance of mAbs targeting the conserved RBD of H2N2 viruses may have been prevalent on a population level in the 1960s, explaining why viruses of this influenza A subtype only circulated in humans from 1957 until 1968.


Subject Category: E. Innate and adaptive immunity to infections, including vaccine immunology

Jens C. Krause, M.D.1, Tshidi Tsibane, Ph.D.2, Chelsey J. Huffman1, David Blum, Ph.D.1, Kathryn Edwards, MD, FIDSA1, Christopher F. Basler, Ph.D.2 and James E. Crowe Jr., MD, FIDSA3, (1)Pediatrics, Vanderbilt University Medical Center, Nashville, TN, (2)Microbiology, Mount Sinai School of Medicine, New York City, NY, (3)Pediatrics and Microbiology and Immunology, Vanderbilt University, Nashville, TN

Disclosures:

J. C. Krause, None

T. Tsibane, None

C. J. Huffman, None

D. Blum, None

K. Edwards, None

C. F. Basler, None

J. E. Crowe Jr., None

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