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.

Conflict of interest statement

The authors report no conflicts of interest pertaining to the conduct and reporting of this clinical trial

Declaration of interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Copyright © 2019 Elsevier Ltd. All rights reserved.

Figures

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

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

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).