The first human trial of a prefusion-closed stabilized HIV-1 Env trimer vaccine found that Trimer 4571 was well tolerated and elicited an immunogenic response. These findings were published in eClinicalMedicine.
This single site, open-label, dose-escalation, randomized phase 1 clinical trial enrolled 16 healthy, HIV-negative adults. Participants were randomly assigned in a 1:1 fashion to receive either a subcutaneous or intramuscular (IM) injection of the Trimer 4571 vaccine, administered at a dose of 100 or 500 mcg at weeks 0, 8, and 20. The primary outcomes were the safety tolerability of Trimer 4571; secondary outcomes were vaccine-induced antibody responses among the participants.
Among the 16 participants, the mean age was 33.0 (range, 22.0-48.0) years, 62.5% were women, and 62.5% were White.
The majority of local and systemic adverse events (AEs) following vaccination were of mild to moderate severity, with the exception of severe erythema over the injection site in 1 participant. Of solicited AEs, 14 (88%) participants had mild tenderness at the injection site and 6 (38%) had mild myalgia. Ten unsolicited AEs were attributed to vaccination, all of which resolved without sequelae.
Vaccine-induced seropositivity occurred among 7 participants who were negative for HIV infection by polymerase chain reaction (PCR) testing. Of these participants, 6 received the 500-mcg dose of the Trimer 4571 vaccine. Seropositivity appeared after sequential vaccination and was resolved among all participants with sufficient data.
Trimer 4571-specific antibodies were detected among all participants 2 weeks following receipt of the second vaccine dose, with the greatest antibody response observed among those who received the 500-mcg dose by IM injection. At week 22, geometric mean (GM) titers were 50,950 and 12,500 among participants in the 500-mcg dose IM group and those in the 100-mcg dose IM group, respectively. Further analysis at week 22 showed GM titers of, 8892 for participants in the 100-mcg dose subcutaneous group vs 19,699 for those in the 500-mcg dose subcutaneous group. All individuals had significantly higher titers compared with baseline.
All participants had a significant increase in Trimer 4571-specific antibodies 2 weeks after receipt of their final vaccine dose (P <.0001).
Using a panel of 18 Env-pseudoviruses from additional HIV-1 clades, Trimer 4571 was found to have glycan shield holes, eliciting no neutralizing activity against the majority of pseudoviruses.
The major limitation of this study was the small sample size. These findings should be confirmed in a larger trial.
According to the researchers, “data from this trial and others serve as contributing steps in the effort to develop an effective HIV-1 vaccine.”
Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.
Houser KV, Gaudinski MR, Happe M, et al. Safety and immunogenicity of an HIV-1 prefusionstabilized envelope trimer (Trimer 4571) vaccine in healthy adults: A first-in-human open-label, randomized, dose-escalation, phase 1 clinical trial. eClinicalMedicine. 2022;101477. doi:10.1016/j.eclinm.2022.101477