An avian influenza H7 DNA priming vaccine is safe and immunogenic in a randomized phase I clinical trial

Abstract

A novel avian influenza subtype, A/H7N9, emerged in 2013 and represents a public health threat with pandemic potential. We have previously shown that DNA vaccine priming increases the magnitude and quality of antibody responses to H5N1 monovalent inactivated boost. We now report the safety and immunogenicity of a H7 DNA-H7N9 monovalent inactivated vaccine prime-boost regimen. In this Phase 1, open label, randomized clinical trial, we evaluated three H7N9 vaccination regimens in healthy adults, with a prime-boost interval of 16 weeks. Group 1 received H7 DNA vaccine prime and H7N9 monovalent inactivated vaccine boost. Group 2 received H7 DNA and H7N9 monovalent inactivated vaccine as a prime and H7N9 monovalent inactivated vaccine as a boost. Group 3 received H7N9 monovalent inactivated vaccine in a homologous prime-boost regimen. Overall, 30 individuals between 20 to 60 years old enrolled and 28 completed both vaccinations. All injections were well tolerated with no serious adverse events. 2 weeks post-boost, 50% of Group 1 and 33% of Group 2 achieved a HAI titer ≥1:40 compared with 11% of Group 3. Also, at least a fourfold increase in neutralizing antibody responses was seen in 90% of Group 1, 100% of Group 2, and 78% of Group 3 subjects. Peak neutralizing antibody geometric mean titers were significantly greater for Group 1 (GMT = 440.61, p < 0.05) and Group 2 (GMT = 331, p = 0.02) when compared with Group 3 (GMT = 86.11). A novel H7 DNA vaccine was safe, well-tolerated, and immunogenic when boosted with H7N9 monovalent inactivated vaccine, while priming for higher HAI and neutralizing antibody titers than H7N9 monovalent inactivated vaccine alone.

Fig. 1

CONSORT flow diagram of the trial. Consolidated standards of reporting trials (CONSORT) diagram delineates study enrollment of 30 subjects who were randomized to three study groups

Fig. 2

Induction of H7-specific antibodies following three different prime-boost regimens. HAI = hemagglutination inhibition assay. Geometric mean titers and 95% confidence intervals are shown 2 weeks following H7N9 boost vaccination. Group 1 received H7 DNA at day 0 and H7N9 MIV at week 16. Group 2 received both H7 DNA and H7N9 MIV prime at day 0 and H7N9 MIV at week 16. Group 3 received H7N9 MIV at day 0 and at week 16. Groups with statistically significant responses are marked with corresponding p-values (Student’s t-test in log measurements)

Fig. 3

Neutralizing antibody responses (ID80) by group assignment. Geometric mean titers and 95% confidence intervals are shown at baseline, the day of boost, and 2 weeks following the H7N9 boost. Group 1 received H7 DNA at day 0 and H7N9 MIV at week 16. Group 2 received both H7 DNA and H7N9 MIV prime at day 0 and H7N9 MIV at week 16. Group 3 received H7N9 MIV at day 0 and at week 16. Groups with statistically significant responses are marked with corresponding p-values (Student’s t-test in log measurements)