Phase I clinical evaluation of seasonal influenza hemagglutinin (HA) DNA vaccine prime followed by trivalent influenza inactivated vaccine (IIV3) boost

Abstract

Annual influenza vaccination reduces the risks of influenza when the vaccines are well matched to circulating strains, but development of an approach that induces broader and more durable immune responses would be beneficial. We conducted two companion Phase 1 studies, VRC 307 and VRC 309, over sequential seasons (2008–2009 and 2009–2010) in which only the influenza B strain component of the vaccines differed. Objectives were safety and immunogenicity of prime–boost vaccination schedules. A schedule of DNA vaccine encoding for seasonal influenza hemagglutinins (HA) prime followed by seasonal trivalent influenza inactivated vaccine (IIV3) boost (HA DNA–IIV3) was compared to placebo (PBS)–IIV3 or IIV3–IIV3. Cumulatively, 111 adults were randomized to HA DNA–IIV3 (n = 66), PBS–IIV3 (n = 25) or IIV3–IIV3 (n = 20). Safety was assessed by clinical observations, laboratory parameters and 7-day solicited reactogenicity. The seasonal HA DNA prime–IIV3 boost regimen was evaluated as safe and well tolerated. There were no serious adverse events. The local and systemic reactogenicity for HA DNA, IIV and placebo were reported predominantly as none or mild within the first 5 days post-vaccination. There was no significant difference in immunogenicity detected between the treatment groups as evaluated by hemagglutination inhibition (HAI) assay. The studies demonstrated the safety and immunogenicity of seasonal HA DNA–IIV3 regimen, but the 3–4 week prime–boost interval was suboptimal for improving influenza-specific immune responses. This is consistent with observations in avian H5 DNA vaccine prime–boost studies in which a long interval, but not a short interval, was associated with improved immunogenicity. Trial Registration: NCT00858611 for VRC 307 and NCT00995982 for VRC 309.

Safety and immunogenicity of investigational seasonal influenza hemagglutinin DNA vaccine followed by trivalent inactivated vaccine administered intradermally or intramuscularly in healthy adults: An open-label randomized phase 1 clinical trial

“…Local reactogenicity was mild to moderate in severity, with higher frequencies of pain/tenderness, swelling, and redness following DNA vaccination by Biojector compared to IIV3 by either administration route, and higher frequencies of redness and swelling following IIV3 administration by the ID route compared to the IM route. These findings are consistent with previous clinical trials [21, 26, 36]. Overall, all vaccine regimens were found to be safe and well tolerated.…”

A novel DNA and protein combination COVID-19 vaccine formulation provides full protection against SARS-CoV-2 in rhesus macaques

“…This is presumably due to the fact that DNA immunization is good at inducing an antigen-specific B cell response while protein immunization can further stimulate activated antigenspecific B cells to produce large amounts of desired antibodies. This heterologous DNA prime-protein boost strategy has been highly immunogenic in human studies with HIV or influenza vaccines [36][37][38][39]. We have adopted the same concept in the current study to test whether co-delivery of DNA and protein COVID-19 vaccines can achieve the same level and quality of protective immune responses as the sequential DNA prime and protein boost approach.…”

A Review of DNA Vaccines Against Influenza

“…Similar results have reported using DNA vaccines to prime LAIV in ferrets ( 104 ) and recombinant HA-protein vaccine in chickens ( 105 ). However, human trials applying this strategy against circulating seasonal influenza failed to significantly improve seroconversion compared to TIV alone ( 106 , 107 ).…”