Immune responses that are associated with a decreased risk of infection are called correlates of protection (CoP). Clinical trials that measure vaccine-induced antibody and cell-mediated immune responses help to define CoP to HIV, which are necessary to assess the efficacy of a promising HIV vaccine candidate. A pilot study led by senior authorsGeorgia Tomaras and Peter Gilbert and first authors Scott Neidich, Youyi Fong and Shuying Li of the NIAID-fundedHIV Vaccine Trials Network (HVTN) demonstrated that an increase in three antibody-mediated immune responses (antibody-mediated Fcƴ receptor [FcgR] recruitment, antibody-dependent cellular phagocytosis [ADCP], and anti-Env IgG3) correlated with a decrease in HIV transmission.
To date, only the RV144/Thai trial has demonstrated moderate efficacy for an experimental HIV vaccine. RV144 identified two primary immune correlates – IgG antibodies to the variable regions of HIV Env correlated with decreased risk of HIV transmission, and plasma IgA to Env correlated with decreased vaccine efficacy. As only one HIV vaccine trial has shown efficacy thus far, the RV144 immune correlates should be corroborated in an independent study to confirm the CoP are true surrogate markers for protection from HIV acquisition.
The HVTN 505 trial tested a DNA and adenovirus 5 (Ad5) vaccine regimen in men at risk of HIV acquisition in the Americas. Despite not demonstrating HIV vaccine efficacy, HVTN 505 can provide insight into possible CoP by comparing participants who were protected with those who acquired HIV during the study. The new pilot study set out to determine whether antibody Fc effector functions observed in HVTN 505 correlated with decreased risk of HIV transmission. The results were published in The Journal of Clinical Investigation.