Many infants whose mothers are infected with HIV are protected from acquiring the virus, but the reasoning behind this is controversial. Researchers at Duke Medicine have identified data on an antibody response previously discounted as being inadequate to confer protection. The data were published in the July 1, 2015, issue of the Journal of Clinical Investigation.
Perinatal transmission, also called mother-to-child transmission, accounts for approximately 250,000 annual HIV infections worldwide, despite expanded access to antiretroviral drug regimens in low-resource settings. Ongoing challenges with access to medication, late initiation of the drug regimens during pregnancy, and acute maternal infection during pregnancy and breastfeeding all contribute to the ongoing transmission rate.
However, even in the absence of antiretroviral drug regimens, most newborns of mothers infected with HIV are naturally protected, despite their chronic exposure to the virus. Thus, the Duke research team sought to determine why some infants become infected and others do not.
“We know that mothers pass antibodies to fetuses in utero, but a true understanding of how maternal antibodies contribute to protection had never been established,” explains lead author Sallie Permar, MD, PhD, an associate professor of pediatrics at Duke.
Permar and colleagues at the Duke Human Vaccine Institute and the Fred Hutchison Cancer Research Center in Seattle analyzed data from a US study conducted in the 1990s that predated therapies such as zidovudine. That study included mothers and babies and yielded information about risk factors and transmission rates in a pretreatment environment.
Among mothers whose babies were shielded from infection, the researchers found a strong antibody response to the third variable (V3) region on the HIV envelope originally considered too variable and inaccessible to be a relevant target for a neutralizing antibody.
Permar notes this finding was surprising. “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. And,” she adds, “there are current HIV vaccine candidates, such as recombinant HIV envelope protein immunization, in early stage clinical testing that can elicit this type of response.”
Permar says that the results of this study raise a compelling question as to why the V3 neutralizing antibody response may appear to reduce the rate of perinatal transmission, yet it is not protective in other modes of HIV transmission.
“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,” elucidates Permar. “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.”
Permar says that additional research at Duke will focus on testing the ability of new, experimental vaccines for HIV to increase the rate of response of this potentially protective antibody in mothers in order to neutralize HIV and protect the infant.
M. Anthony Moody, MD, coauthor and chief medical officer at the Duke Human Vaccine Institute, says he hopes these data will help create a vaccine capable of preventing all perinatal HIV transmission.
“These antibodies are the type that our current experimental HIV vaccines can boost,” notes Moody. “We may be closer than we were previously to testing a vaccine that can induce this type of common, HIV-specific antibody response for its ability to protect infants.”