TUESDAY, SEPTEMBER 27, 2016

Antibody response linked to decreased mother-to-child HIV transmission

Sallie Permar
Despite wide access to drug regimens and therapies that can interrupt transmission, an estimated 250,000 HIV infections each year worldwide are mother-to-child.

Reasons for this are ongoing problems getting drugs to patients, initiating the drug therapy too late in pregnancy, acute maternal infection during pregnancy, and breastfeeding.

"We know that mothers pass antibodies to fetuses in-utero, but a true understanding of how maternal antibodies were contributing to protection had never been established," Sallie Permar, associate professor of pediatrics at Duke University and lead author of a study published online this month in the Journal of Clinical Investigation, said.

Even without drug therapy, most newborns are naturally protected from HIV. Permar's research team at Duke recently did a study in hopes of discovering why some babies of HIV-infected mothers get the virus and others do not. Permar and her colleagues at the Duke Human Vaccine Institute and the Fred Hutchison Cancer Research Center studied and analyzed data from the 1990s, which was before therapies such as AZT were available.

The team profiled the immune responses of mothers in the early study. The mothers whose babies did not become infected all had a strong antibody response to a specific area on the HIV virus envelope -- the HIV V3 loop.

"That was very surprising," Permar said. "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 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 said the study raised questions as to why the V3 neutralizing antibody response seemed to be sufficient to decrease mother-to-child transmission, but would not protect patients in other modes of 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," 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."

Research at Duke will continue, and will focus on more recent, experimental HIV innoculations that could provide protective antibody response in expectant mothers who could protect their babies.

"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," M. Anthony Moody, a co-author and chief medical officer in the Duke Human Vaccine Institute, said.

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