title: Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies.
abstract: During seasonal influenza epidemics, disease burden is shouldered predominantly by the very young and the elderly. Elderly individuals are particularly affected, in part because vaccine efficacy wanes with age. This has been linked to a reduced ability to induce a robust serum antibody response. Here, we show that this is due to reduced quantities of vaccine-specific antibodies, rather than a lack of antibody avidity or affinity. We measured levels of vaccine-specific plasmablasts by ELISPOT 1 week after immunization of young and elderly adults with inactivated seasonal influenza vaccine. Plasmablast-derived polyclonal antibodies (PPAbs) were generated from bulk-cultured B cells, while recombinant monoclonal antibodies (re-mAbs) were produced from single plasmablasts. The frequency of vaccine-specific plasmablasts and the concentration of PPAbs were lower in the elderly than in young adults, whereas the yields of secreted IgG per plasmablast were not different. Differences were not detected in the overall vaccine-specific avidity or affinity of PPAbs and re-mAbs between the 2 age groups. In contrast, reactivity of the antibodies induced by the inactivated seasonal influenza vaccine toward the 2009 pandemic H1N1 virus, which was not present in the vaccine, was higher in the elderly than in the young. These results indicate that the inferior antibody response to influenza vaccination in the elderly is primarily due to reduced quantities of vaccine-specific antibodies. They also suggest that exposure history affects the cross-reactivity of vaccination-induced antibodies.
authors.affiliation: Department of Immunology and Microbiology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Sanae
authors.initials: S
authors.lastname: Sasaki
authors.forename: Meghan
authors.initials: M
authors.lastname: Sullivan
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Narvaez
authors.forename: Tyson H
authors.initials: TH
authors.lastname: Holmes
authors.forename: David
authors.initials: D
authors.lastname: Furman
authors.forename: Nai-Ying
authors.initials: NY
authors.lastname: Zheng
authors.forename: Madhuri
authors.initials: M
authors.lastname: Nishtala
authors.forename: Jens
authors.initials: J
authors.lastname: Wrammert
authors.forename: Kenneth
authors.initials: K
authors.lastname: Smith
authors.forename: Judith A
authors.initials: JA
authors.lastname: James
authors.forename: Cornelia L
authors.initials: CL
authors.lastname: Dekker
authors.forename: Mark M
authors.initials: MM
authors.lastname: Davis
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Wilson
authors.forename: Harry B
authors.initials: HB
authors.lastname: Greenberg
authors.forename: Xiao-Song
authors.initials: XS
authors.lastname: He
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000737:chemistry*; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000915:Antibody Affinity; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry; D007074:Immunoglobulin G / Q000737:chemistry; D007252:Influenza Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D007251:Influenza, Human / Q000517:prevention & control; D010950:Plasma Cells / Q000378:metabolism; D055815:Young Adult
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines