One of the more devastating casualties of the HIV crisis that earnestly began in the 1980s has been children born to HIV-infected mothers.

Stripped of any choice, these victims will bear the lengthiest burdens, needing to be nestled on antiretroviral treatment for the rest of their natural lives to stave off the virus. Though efforts to preemptively head off the chance of transmission from mother to child in-utero or through postnatal contact (breastfeeding) through medication can be successful more than 95 percent of the time, according to the World Health Organization (WHO), there are still many children who needlessly fall into the chasm. These cases are largely the result of inadequate resources in low-to-middle income countries to properly screen and treat infected mothers, and represent an enduring challenge to stemming the tide of HIV transmission. Yet, according to the WHO, as many as 55 to 85 percent of children born to HIV-positive mothers somehow do not develop the disease. It’s a mystery that researchers from Duke Medicine, in a study published in the Journal of Clinical Investigation, may have just discovered the answer to.

Looking back in time, the authors studied data from an earlier study on HIV transmission between mothers and children in the 1990s, prior to the practice of routine treatment. The study provided information on the types of antibodies present in both. From there, the current authors were to identify an antibody response to a region on the viral envelope of HIV (the V3 loop) that predicted a lower risk of mother-to-child transmission. It was one that had been previously set aside as irrelevant to protection against HIV in adults, though there had been some preliminary support for this particular effect. "That was very surprising," lead author and associate professor of pediatrics at Duke Dr. Sallie Permar said in a press statement, "because this type of weak neutralizing antibody response, which had previously been thought to be inconsequential for HIV transmission, could potentially be effective in preventing mother-to-child transmission."

Other experiments using V3-specific immune cells from an HIV-infected mother who hadn’t transmitted the virus were effective at neutralizing various strains of the virus, though only those particularly weak already. That somewhat furthers the mystery as to why the antibody response only works in mothers, but the researchers have some theories. "The difference in mother-to-infant transmission might be that the infant is only being exposed to the mother's virus, and the infant is born with antibodies that are transferred from the mother," Permar said. "The presence of antibodies that were raised against the mother's virus prior to exposure to the same virus makes the infant transmission setting very different from that of other modes of HIV transmission. So how well the mother's antibody can neutralize her own virus could be the key to whether the baby is infected."

Noting that research efforts may soon be able to elicit these reactions from the immune systems of mothers, the authors and their Duke colleagues are hopeful their findings can point to productive new areas to take treatments already in the pipeline. "We hope this will be a major clue to making a vaccine to effectively prevent all mother-to-child HIV transmission, since these antibodies are the type that our current experimental HIV vaccines can boost," said co-author Dr. M. Anthony Moody, chief medical officer in the Duke Human Vaccine Institute. "For protecting unborn and newborn children, we may be closer to testing a vaccine that can induce this type of common HIV-specific antibody response for its ability to protect infants than previously thought."

Source: Permar S, Fong Y, Vandergrift N, et al. Maternal HIV-1 envelope–specific antibody responses and reduced risk of perinatal transmission. Journal of Clinical Investigation. 2015.