Safety and immunogenicity of an HIV-1 prefusion-stabilized

Advances in therapeutic drugs have increased the life expectancy of people infected with HIV, but the need for an effective vaccine remains. We evaluated the safety and immunogenicity of the HIV-1 vaccine, Trimer 4571 (BG505 DS-SOSIP.664) adjuvanted with aluminum hydroxide (alum), in seronegative adults.

We conducted a phase I, randomized, open-label, dose-escalation trial at the National Institutes of Health Clinical Center in Bethesda, MD, USA. Eligible participants were healthy, HIV-negative adults between the ages of 18 and 50. Participants were randomized 1:1 to receive Trimer 4571 adjuvanted with 500 mcg alum subcutaneously (SC) or intramuscularly (IM) at weeks 0, 8, and 20 in increasing doses of 100 mcg or 500 mcg. The primary objectives were to assess the safety and tolerability of Trimer 4571 with a secondary objective to assess vaccine-induced antibody responses. Primary and safety endpoints were assessed in all participants who received at least one dose of Trimer 4571. Trial results were summarized using descriptive statistics. This trial is registered with, NCT03783130.

Between March 7 and September 11, 2019, 16 HIV-negative participants were enrolled, including six (38%) men and ten (62%) women. All participants received three doses of Trimer 4571. Solicited reactogenicity was mild to moderate in severity, with one isolated case of severe redness at the injection site (6%) after a third SC administration of 500 mcg.

The most commonly reported solicited symptoms included mild injection site tenderness in 14 (88%) and mild myalgia in six (38%) participants. The most common unsolicited adverse event attributed to vaccination was mild injection site pruritus in six (38%) participants. Vaccine-induced seropositivity occurred in seven (44%) participants and resolved in all but one (6%).

No unfortunate incident occurred. Specific binding antibodies to trimer 4571 were detected in all groups two weeks after the end of the diet, mainly concentrated on the basis of trimer without glycan. Neutralizing antibody activity was limited to the 500 mcg dose groups.Trimer 4571 was safe, well tolerated and immunogenic in this first-in-man trial. Although this phase 1 trial is limited in size, our results inform and support further evaluation of prefusion-stabilized HIV-1 envelope trimers as a component of vaccine design strategies to generate broadly neutralizing antibodies against HIV-1.

Intramural Research Program of the Center for Vaccine Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.