An ongoing challenge for HIV vaccine research has been the identification of the ideal vaccine regimen for the induction of an effective immune response while maintaining safety and tolerability of the regimen for recipients. Many phase I clinical trials have been initiated by the HIV Vaccine Trials Network to study various combinations of vaccine products to assess the resulting immunogenicity and tolerability. HVTN protocol 069 evaluated the safety and immunogenicity of a combination candidate vaccine consisting first of DNA plasmid vaccine administered intramuscularly, followed by a recombinant adenovirus serotype 5 (rAd5)-vectored HIV-1 vaccine boost administered intramuscularly, intradermally or subcutaneously. Participants received three doses of the DNA vaccine, followed by one boosting dose of the rAd5 vaccine via one of the three routes of administration. Local and systemic responses were monitored, and the resulting immune responses were evaluated to determine the immunogenicity of the vaccine and determine which route of administration for the rAd5 vaccine resulted in the most robust immune responses. The trial was evaluated by VIDD staff scientists Cecilia Morgan and Olivier Defawe, VIDD assistant member Dr. Li Qin, VIDD co-director Julie McElrath and colleagues.
This trial was halted early due to the results of the Step study, which used a similar recombinant adenovirus serotype 5 vaccine, but two-thirds of participants completed the entire regimen and were able to be evaluated. Following the rAd5 boost, there were significant differences in the severity of headache, pain, and erythema based on route of administration, with lower frequencies of these side effects in the intramuscular group than in the other two groups. In contrast, the regimen’s immunogenicity, as measured by antibody levels and HIV-specific cellular responses, was not significantly different between the study arms. Although statistical power was limited due to the reduced sample size, based on these findings the intramuscular route of administration for the rAd5 vaccine is preferable given the reduced frequency of reactogenicity and lack of evidence for improved immunological benefit when using the other routes of administration.
Koblin BA, Casapia M, Morgan C, Qin L, Wang ZM, Defawe OD, Baden L, Goepfert P, Tomaras GD, Montefiori DC, McElrath MJ, Saavedra L, Lau CY, Graham BS; NIAID HIV Vaccine Trials Network. Safety and immunogenicity of an HIV adenoviral vector boost after DNA plasmid vaccine prime by route of administration: a randomized clinical trial. PLoS ONE. 2011;6(9):e24517.