Globally each year, 150,000 infants are infected with human immunodeficiency virus, commonly known as HIV—primarily through mother-to-child transmission. Improving outcomes for those infected infants is important, especially because of limited access to antiretroviral therapy. Without the treatment, the risk of transmission during the breastfeeding period is between 10% and 20%, depending on the duration of breastfeeding. That data suggests an infant has natural immune mechanisms that protect against HIV acquisition—which could be a path to research for a potential future HIV vaccine.
According to new research from Boston Medical Center, the immune response that's associated with protection against HIV in infants is known as antibody-dependent cellular cytotoxicity (ADCC). Infants with high levels of ADCC against their mother's strain of HIV are less likely to get HIV through breast milk and have lower rates of morbidity and death even without antiretroviral therapy, the study shows. The response means infants passively acquire maternal antibodies before and while they are consistently exposed to the virus, and they acquire HIV at a lower frequency than typically expected, considering the long duration of viral exposure in utero and during breastfeeding.
Mother-to-child HIV transmission research
Published in Cell Reports Medicine, this study involved researchers examining samples of patient breast milk and maternal plasma from mother-infant pairs who were enrolled from a previous mother-to-child-transmission clinical trial in Malawi. All mothers had chronic HIV infection and had breastfed their babies, who did not have HIV at the start of the study. The 16 mothers who transmitted HIV had their antibody functions compared to the 26 mothers who did not transmit the infection. Similarly, the infants who acquired HIV from their mothers were compared to those infants who did not.
Researchers evaluated the ADCC present in both pre-transmission infant and maternal plasma and breast milk against existing maternal HIV-1 variants. The infants who were exposed yet uninfected had higher ADCC and a combination of ADCC and neutralizing antibody responses against their corresponding mother's strains, compared to infants who were exposed and infected. The infected infants with high ADCC function also had lower morbidity and mortality up to one year after birth.
"Similar to COVID-19, it is generally believed that if people have pre-existing neutralizing antibodies against HIV, it will protect them from acquiring HIV," says Manish Sagar, MD, an infectious diseases physician at BMC and corresponding author on this study. "Unlike COVID-19, however, this research demonstrates that the presence of neutralizing antibodies in exposed individuals does not protect from HIV transmission."
A new potential target for HIV vaccine research
Instead, BMC's findings indicate that ADCC could be a potential new target for future vaccine research. ADCC, more than neutralizing antibodies, associates with lower mother-to-child transmission and decreased post-infection infant morbidity.
Therefore, the researchers recommend that HIV vaccine efforts should include a focus on enhancing ADCC responses in highly exposed, at-risk individuals. Because current immunogens have been unable to elicit neutralizing antibodies, inducing ADCC responses may be a more feasible target.
"HIV vaccine efforts have been primarily focused on eliciting neutralizing antibodies," says Sagar. "The results of this study suggest that there are additional immune factors that may be associated with protection against HIV transmission."