Researchers are urging caution when it comes to the use of adenovirus type-5 (Ad5) vectored vaccines for COVID-19.
As the race to approval of a safe and effective vaccine for coronavirus disease 2019 (COVID-19) continues, a group of researchers is warning some of these vaccines could make patients more susceptible to contracting HIV.
Writing in The Lancet, the researchers are urging caution when it comes to the use of adenovirus type-5 (Ad5) vectored vaccines for COVID-19, recalling their research from a decade ago on an Ad5 vectored vaccine in 2 HIV vaccine trials.
“On the basis of these findings, we are concerned that use of an Ad5 vector for immunisation against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could similarly increase the risk of HIV-1 acquisition among men who receive the vaccine,” wrote the researchers. “Both the HIV and COVID-19 pandemics disproportionately affect vulnerable populations globally. Roll-out of an effective SARS-CoV-2 vaccine globally could be given to populations at risk of HIV infection, which could potentially increase their risk of HIV-1 acquisition.”
The group’s ”cautionary tale” stems from the Step and Phambili phase 2b trials that studied the efficacy of an Ad5 vectored HIV-1 vaccine in preventing HIV infection. Across both international studies, they found that the vaccine actually increased the risk of HIV among the vaccinated men.
The findings from the Phambili study, in particular, have important implications for the use of the vaccines in COVID-19, according to the researchers, as findings from this study showed that heterosexual men receiving the Ad5 vectored vaccine faced a consistently increased risk of HIV infection. Notably, this increased risk appeared to be limited to men, with women not having an observed increase of infection in the study.
In the Step trial, the risk of acquiring HIV was particularly high among men who were uncircumcised and Ad5 seropositive men who reported having unprotected anal sex with a partner who was HIV seropositive or who had unknown serostatus as baseline.
Of note, the vaccine in both studies did not have the HIV envelope. Meanwhile, in another study that used a DNA prime and an Ad5 vector, both of which had the HIV envelope, there was no observed increase in HIV infection.
The reason for the observed increase in HIV risk remains uncertain, although several follow-up studies have suggested a potential explanation, according to the researchers.
“The vaccine was highly immunogenic in the induction of HIV-specific CD4 and CD8 T cells; however, there was no difference in the frequency of T-cell responses after vaccination in men who did and did not later become infected with HIV in the Step Study,” they wrote. “These findings suggest that immune responses induced by the HIV-specific vaccine were not the mechanism of increased acquisition. Participants with high frequencies of preimmunisation Ad5-specific T cells were associated with a decreased magnitude of HIV-specific CD4 responses and recipients of the vaccine had a decreased breadth of HIV-specific CD8 responses, suggesting that pre-existing Ad5 immunity might dampen desired vaccine-induced responses.”
Other exploratory studies have indicated that the vaccine enhances HIV replication in CD4 T cells or that Ad5-specific CD4 T cells could be more susceptible to HIV infection.
Buchbinder SP, McElrath MJ, Dieffenback C, Corey L. Use of adenovirus type-5 vectored vaccines: a cautionary tale. Lancet. Published online October 19, 2020.doi:10.1016/S0140-6736(20)32156-5