1. From this small randomized, double-blinded, placebo controlled trial, two novel adenovirus-based human immunodeficiency virus (HIV) vaccinations were safe, well-tolerated, and immunogenic.
2. Anti-HIV antibody responses were observed when participants received the same vaccine as a priming dose and booster, or when patients received first one and then the other vaccine.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Development of a vaccine against HIV has been a major goal in vaccine research. Although several potential vaccines have been tested, none has ultimately proven to be effective at preventing HIV. This study assessed the safety of two novel HIV vaccines, as well as their ability to generate an immune response against a key protein specific to HIV from an initial vaccination and a booster. For some participants, one vaccine was used for both initial vaccination and booster; for others, one vaccine was used for the initial vaccination, and the other vaccine was used for the booster. Another group of participants received placebo vaccinations. Generally, both vaccines were found to be safe, although they caused slightly more severe but brief adverse reactions than placebo. Both vaccines were also found to spur creation of antibodies against the HIV protein, a key requirement for developing immunity to the virus. Antibody generation occurred whether participants received the same vaccine twice (as initial and booster vaccinations), or one and then the other. The primary limitation of this study was that it was a relatively small trial that did not test the efficacy of these vaccines at preventing HIV, but rather sought to demonstrate safety and ability to generate short-term immune responses against the virus. The duration of this immune response and its ability to ultimately prevent HIV infection remain unknown. Nevertheless, this study is a promising step in the evaluation of these two new vaccines, and suggests that these vaccines may be good candidates for longer-term efficacy trials.
Relevant Reading: A Global Approach to HIV-1 Vaccine Development
In-Depth [randomized controlled trial]: This trial compared the safety and immunogenicity of two vaccines containing an HIV-1 clade A gene coding a modified gp140 envelope protein. One vaccine used adenovirus serotype 26 (Ad26) as a vector, while the other used adenovirus serotype 35 (Ad35). The vaccine was delivered as a priming dose and then a booster either 3 or 6 months later; homologous (Ad26-Ad26 or Ad35-Ad35) and heterologous (Ad26-Ad35 or Ad35-Ad26) prime/booster vaccine pairings were tested. Overall, no serious adverse events occurred in participants receiving either (or both) vaccine, although participants receiving a vaccine were more likely to have a brief but moderate or severe systemic reaction (36.4%, 95%CI 29.2% to 44.1%) compared to participants receiving placebo (20.5%, 95%CI 9.8% to 35.3%; p = 0.045). All prime/booster vaccine combinations generated significantly higher anti-HIV Env antibody titers than placebo (p < 0.001). Use of Ad26 as a priming dose and Ad35 as a booster yielded higher anti-HIV Env antibody titers compared to use of Ad35 first, followed by Ad26. The presence of neutralizing antibodies against adenovirus did not blunt the immunogenicity of initial or booster vaccines. Although larger, long-term efficacy trials must be conducted before the true potential of these vaccines can be assessed, they nevertheless show initial promise in both homologous and heterologous prime/booster combinations.
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