Mother–Infant HIV Transmission: Do Maternal HIV-Specific Antibodies Protect the Infant?

MTCT has been a rich source of information for prevention research; it has demonstrated the benefit of using ARVs to block transmission and it has also provided insights into the potential of antibodies to prevent HIV infection. However, understanding the factors that lead to the majority of HIV-exposed infants eluding infection is challenging because the determinants of risk are clearly multifactorial. In that regard, other immune responses may contribute to this protection, including cellular immune mechanisms and innate factors [1], [2]. Studies of immune correlates of protection are also complicated by the dynamic nature of HIV and the immune response to it. While the current state of knowledge suggests that antibody-mediated protection may not be the major factor in determining if an infant acquires HIV from their mother, it may play a role. There is some provocative but relatively limited evidence that antibodies may protect infants via ADCC. In the case of Nabs, several small studies have shown a correlation between Nabs and protection, but results of studies on this topic are variable and would benefit from larger studies focused specifically on the window of transmission. There is perhaps better evidence that antibodies contribute to blocking virus variants that are highly sensitive to neutralization, suggesting that the Nabs elicited in a typical infection may not have adequate breadth and/or potency to prevent transmission of the harder-to-neutralize viruses. This may be a peculiarity of MTCT, where escape variants elicited specifically to maternal antibodies are often present. MTCT could therefore provide insights on the potency of antibody needed for protection if we can understand which subset of maternal variants are blocked by antibodies and if some mothers have antibodies of sufficient breadth and potency to completely prevent infant infection. Understanding how much antibody is needed to block infant infection could be invaluable in helping guide vaccine design, where the bar for eliciting antibody-based protection in humans is poorly defined.