title: B cell response and hemagglutinin stalk-reactive antibody production in different age cohorts following 2009 H1N1 influenza virus vaccination.
abstract: The 2009 pandemic H1N1 (pH1N1) influenza virus carried a swine-origin hemagglutinin (HA) that was closely related to the HAs of pre-1947 H1N1 viruses but highly divergent from the HAs of recently circulating H1N1 strains. Consequently, prior exposure to pH1N1-like viruses was mostly limited to individuals over the age of about 60 years. We related age and associated differences in immune history to the B cell response to an inactivated monovalent pH1N1 vaccine given intramuscularly to subjects in three age cohorts: 18 to 32 years, 60 to 69 years, and ≥70 years. The day 0 pH1N1-specific hemagglutination inhibition (HAI) and microneutralization (MN) titers were generally higher in the older cohorts, consistent with greater prevaccination exposure to pH1N1-like viruses. Most subjects in each cohort responded well to vaccination, with early formation of circulating virus-specific antibody (Ab)-secreting cells and ≥4-fold increases in HAI and MN titers. However, the response was strongest in the 18- to 32-year cohort. Circulating levels of HA stalk-reactive Abs were increased after vaccination, especially in the 18- to 32-year cohort, raising the possibility of elevated levels of cross-reactive neutralizing Abs. In the young cohort, an increase in MN activity against the seasonal influenza virus A/Brisbane/59/07 after vaccination was generally associated with an increase in the anti-Brisbane/59/07 HAI titer, suggesting an effect mediated primarily by HA head-reactive rather than stalk-reactive Abs. Our findings support recent proposals that immunization with a relatively novel HA favors the induction of Abs against conserved epitopes. They also emphasize the need to clarify how the level of circulating stalk-reactive Abs relates to resistance to influenza.
authors.affiliation: David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA. mark_sangster@urmc.rochester.edu
authors.forename: Mark Y
authors.initials: MY
authors.lastname: Sangster
authors.forename: Jane
authors.initials: J
authors.lastname: Baer
authors.forename: Felix W
authors.initials: FW
authors.lastname: Santiago
authors.forename: Theresa
authors.initials: T
authors.lastname: Fitzgerald
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Ilyushina
authors.forename: Aarthi
authors.initials: A
authors.lastname: Sundararajan
authors.forename: Alicia D
authors.initials: AD
authors.lastname: Henn
authors.forename: Florian
authors.initials: F
authors.lastname: Krammer
authors.forename: Hongmei
authors.initials: H
authors.lastname: Yang
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Luke
authors.forename: Martin S
authors.initials: MS
authors.lastname: Zand
authors.forename: Peter F
authors.initials: PF
authors.lastname: Wright
authors.forename: John J
authors.initials: JJ
authors.lastname: Treanor
authors.forename: David J
authors.initials: DJ
authors.lastname: Topham
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated