HIV Strains Transmitted to Infants Found Resistant to Mother's Antibodies

The clinically relevant findings suggest that infant passive immunization with second-generation broad and potent bNAbs could be an effective strategy to block mother-to-child HIV transmission.

Amit Kumar, PhD

HIV passes from a mother to her child because a few of the viral strains infecting the woman are able to evade attack from protective antibodies in her blood, new research shows.

The discovery might help scientists develop a vaccine to boost immune responses capable of neutralizing these specific HIV-1 variants, say researchers led by Amit Kumar, PhD, and colleagues at Duke University Medical Center in Durham, North Carolina.

“Our findings could help guide development of a new vaccine for pregnant mothers with HIV-1 that could further reduce pediatric HIV infections,” Kumar, a research scientist at Duke Human Vaccine Institute, told MD Magazine. “Such a vaccine would boost maternal antibody attack of HIV-1 variants circulating in a woman’s own blood so that transmission risk is reduced when an infant is exposed to maternal blood during delivery."

Mother-to-child HIV transmission (MTCT) has been dramatically reduced thanks to the advent of antiretroviral therapies (ART). Without ART, about 40% of infants get HIV from their infected mothers, but with ART, the rate of transmission can be as low as 1%—2%.

Even so, more than 150,000 children become infected each year, a number that researchers say remains unacceptably high.

“ART availability in resource-poor areas, adherence to drug regimes, and toxicity to infants becomes a limiting factor in prevention of MTCT of HIV,” Kumar said.

In addition, ART-resistant HIV strains are making it more difficult to prevent mother-to-child-transmission.

“Hence, we need to develop other means to prevent MTCT other than ART,” noted Kumar.

Scientists studying MTCT have suggested that only a few of the genetically diverse variants of HIV carried by a mother go on to infect an infant during pregnancy, childbirth and breastfeeding.

To better identify and understand the strains that a mother transmits to her child, Kumar and colleagues studied 16 women infected with HIV and their infants.

They chose the subjects from the Women and Infants Transmission Study (WITS). This investigation was conducted in the 1990s, before ART was available, eliminating antiretroviral therapy as a potentially complicating factor in the current study.

The team analyzed the blood samples from the mothers and infants, who were infected at delivery, and determined which HIV-1 variants were present for each pair.

Researchers then tested the sensitivity to antibodies in the mother’s blood for all of the HIV variants, either transmitted or not transmitted.

They found that the virus variants infecting the infants were more resistant to antibodies in the mother’s blood than the HIV variants that weren’t passed on, however, the transmitted viruses turned out to be sensitive to other antibodies. These broadly neutralizing HIV-1 antibodies (bNAbs) can block infection by diverse HIV strains, making them a focus of vaccine developers.

“We found that antibodies targeting the mother’s own virus play a major role in selecting transmitted HIV variants,” Kumar said. “Our work also indicated that antibodies targeting the Variable loop 3 (V3) and Membrane Proximal External Region (MPER) region of the HIV envelope can help in preventing MTCT via peripartum mode."

Kumar said that raising antibodies against these regions in an HIV infected pregnant woman might prevent transmission to the infant.

“ART can help keeping HIV infections under control but it is not a cure,” he added. “We still need to develop a vaccine or therapeutic antibodies, which can synergize with ART to prevent MTCT completely.”

The team, which published its findings PLOS Pathogens, is conducting further research.

“In subsequent studies, we are trying to isolate monoclonal antibodies from the maternal blood and test them against the maternal non-transmitted and infant transmitted founder viruses,’’ Kumar concluded.