James Crowe
Faculty Member
Last active: 3/31/2020

Human monoclonal antibodies to pandemic 1957 H2N2 and pandemic 1968 H3N2 influenza viruses.

Krause JC, Tsibane T, Tumpey TM, Huffman CJ, Albrecht R, Blum DL, Ramos I, Fernandez-Sesma A, Edwards KM, GarcĂ­a-Sastre A, Basler CF, Crowe JE
J Virol. 2012 86 (11): 6334-40

PMID: 22457520 · PMCID: PMC3372199 · DOI:10.1128/JVI.07158-11

Investigation of the human antibody response to the 1957 pandemic H2N2 influenza A virus has been largely limited to serologic studies. We generated five influenza virus hemagglutinin (HA)-reactive human monoclonal antibodies (MAbs) by hybridoma technology from the peripheral blood of healthy donors who were born between 1950 and 1968. Two MAbs reacted with the pandemic H2N2 virus, two recognized the pandemic H3N2 virus, and remarkably, one reacted with both the pandemic H2N2 and H3N2 viruses. Each of these five naturally occurring MAbs displayed hemagglutination inhibition activity, suggesting specificity for the globular head domain of influenza virus HA. When incubated with virus, MAbs 8F8, 8M2, and 2G1 each elicited H2N2 escape mutations immediately adjacent to the receptor-binding domain on the HA globular head in embryonated chicken eggs. All H2N2-specific MAbs were able to inhibit a 2006 swine H2N3 influenza virus. MAbs 8M2 and 2G1 shared the V(H)1-69 germ line gene, but these antibodies were otherwise not genetically related. Each antibody was able to protect mice in a lethal H2N2 virus challenge. Thus, even 43 years after circulation of H2N2 viruses, these subjects possessed peripheral blood B cells encoding potent inhibiting antibodies specific for a conserved region on the globular head of the pandemic H2 HA.

MeSH Terms (21)

Adult Animals Antibodies, Monoclonal Antibodies, Viral Chick Embryo Disease Models, Animal Female Hemagglutinin Glycoproteins, Influenza Virus Humans Influenza, Human Influenza A Virus, H2N2 Subtype Influenza A Virus, H3N2 Subtype Mice Mice, Inbred BALB C Middle Aged Molecular Sequence Data Mutation, Missense Orthomyxoviridae Infections RNA, Viral Sequence Analysis, DNA Survival Analysis

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