Safety and Immunogenicity of a Subvirion Monovalent Unadjuvanted Inactivated Influenza A(H3N2) Variant Vaccine in Healthy Persons ≥18 Years Old

Abstract

Background: Variant influenza A(H3N2) viruses (H3N2v) have transmitted recently from pigs to humans in the United States. Vaccines strategies are needed.

Methods: Healthy adults received 2 doses of subvirion H3N2v vaccine (15 µg of hemagglutinin/dose) 21 days apart in this open-label trial. Serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody (Ab) titers were measured before and 8 and 21 days after each dose. Memory B-cell (MBC) responses were assessed.

Results: Vaccine was well tolerated. A total of 40% of subjects had an HAI Ab titer of ≥40 before vaccination. Eight-seven percent (95% confidence interval [CI], 79%-93%) and 73% (95% CI, 63%-81%) of subjects 18-64 years old (98 subjects) and ≥65 years old (90 subjects), respectively, had an HAI titer of ≥40 21 days after dose 1 (P = .01); 51% (95% CI, 41%-61%) and 52% (95% CI, 41%-62%) of younger and older subjects, respectively, developed ≥4-fold rises in titer (P = not significant). Neut Ab response patterns were similar. Geometric mean titers were higher in younger subjects. Dose 2 provided no significant enhancement in responses. Cross-reactive MBCs were detected before vaccination and expanded after vaccination. Preexisting H3N2v-specific MBCs positively correlated with early increases in vaccine-induced Ab.

Conclusions: In most healthy adults, one 15-µg dose of vaccine elicited levels of HAI Abs associated with protection. Studies in children and elderly individuals are indicated to define the immunization needs of these groups.

Clinical trials registration: NCT01746082.

Keywords: H3N2 variant; immune responses; immunization; influenza; pandemic.

Figure 1.

CONSORT (Consolidated Standards of Reporting Trials) diagram of subject disposition.

Figure 2.

Reverse cumulative distribution curves of serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibodies (Abs) following immunization with H3N2v IIV1.

Figure 3.

Memory B-cell (MBC) responses before and after vaccination. A, Relationship of fold change in hemagglutination inhibition (HAI) antibody (Ab) titer against H3N2v 8 and 21 days after vaccination and day 0 MBCs against H3N2v or 2 seasonal H3 strains measured before vaccination (enzyme-linked immunospot MBC assay; n = 20). B, Percentage of H3N2-reactive B cells before vaccination and at day 42 (B-cell transformation method; n = 13 and n = 25 at day 0 and day 42, respectively). Abbreviation: IgG, immunoglobulin G.