Safety and immunogenicity of an 8 year interval heterologous prime-boost influenza A/H7N7-H7N9 vaccination

Abstract

Background: Influenza A/H7N9 viruses are undergoing antigenic drift since their emergence in 2013, and vaccination strategies are needed for pandemic preparedness. Two doses of adjuvanted monovalent inactivated influenza A/H7N9 vaccine (IIV1 A/H7N9) are needed for optimal serological responses. However, administering 2 doses in a pandemic setting might be challenging. We evaluated the immunogenicity of "boosting" with IIV1 A/H7N9 in subjects "primed" 8 years previously with IIV1 A/H7N7.

Methods: We administered 1 booster dose containing 45 mcg of IIV1 A/H7N9 hemagglutinin to 17 recipients of 2 prior doses of IIV1 A/H7N7, and to 10 influenza A/H7-naïve subjects. We tested their post-boosting sera for antibodies (Ab) against homologous influenza A/H7N9 using a hemagglutination inhibition assay; and compared their Ab titers to those in stored sera from recipients of AS03-adjuvanted IIV1 A/H7N9 against 9 strains of influenza A/H7N9 viruses.

Results: The percentage of subjects with Ab titers ≥40 on Days 9 and 29 post boosting, respectively, was 65% and 41% in primed subjects and 10% and 0% in unprimed subjects. The Ab titers in recipients of AS03-adjuvanted IIV1 A/H7N9 were higher than those in the prime-boost group against a panel of influenza A/H7N9 viruses, except for 2 highly pathogenic strains.

Conclusions: Priming with IIV1 A/H7 results in serological responses following a delayed boost with 1 dose of unadjuvanted IIV1 A/H7N9, despite lack of antibody response after the prime. Optimizing prime-boost approaches would benefit pandemic preparedness. ClinicalTrials.gov identifier: NCT02586792.

Keywords: Avian; Influenza; Influenza A/H7N9; Pandemic; Prime-boost; Vaccines.

Figure 1.

Study Flow Chart (CONSORT diagram)

Figure 2.

Hemagglutination inhibition antibody titers following influenza A/H7N9 in A/H7N7 primed and A/N7-naïve individuals for the prime and boost strains. Panel A displays Geometric mean titers (GMT) with corresponding 95% confidence intervals; post-vaccination titers were significantly higher (p<0.05 by Wilcoxon test) for previously primed subjects at all time points for both prime and boost strains. Panel B displays reverse cumulative distributions of HAI and MN titers by post vaccination visit; a reference line is shown at the seroprotective titer (1:40).

Figure 2.

Hemagglutination inhibition antibody titers following influenza A/H7N9 in A/H7N7 primed and A/N7-naïve individuals for the prime and boost strains. Panel A displays Geometric mean titers (GMT) with corresponding 95% confidence intervals; post-vaccination titers were significantly higher (p<0.05 by Wilcoxon test) for previously primed subjects at all time points for both prime and boost strains. Panel B displays reverse cumulative distributions of HAI and MN titers by post vaccination visit; a reference line is shown at the seroprotective titer (1:40).

Figure 3

Hemagglutination inhibition antibody titers (2A) and seroprotection rates (2B) following influenza A/H7N9 vaccine boost (current study) and in stored sera following AS03-adjuvanted influenza A/H7N9 vaccine against 9 influenza A/H7N9 virus strains from epidemic waves 1 and 5. (See Methods section for virus designation).

Figure 3

Hemagglutination inhibition antibody titers (2A) and seroprotection rates (2B) following influenza A/H7N9 vaccine boost (current study) and in stored sera following AS03-adjuvanted influenza A/H7N9 vaccine against 9 influenza A/H7N9 virus strains from epidemic waves 1 and 5. (See Methods section for virus designation).