Researchers Map How HIV Escapes Mother’s Immune Attack to Infect Infants
DURHAM, N.C. -- Mother-to-child transmission of HIV has been reduced dramatically worldwide with the use of anti-retroviral therapies (ART), but even with these effective drugs, approximately 400 babies a day become infected before, during and after birth.
How this happens has been a question that complicates treatment and vaccine development strategies. Now researchers led by the Duke Human Vaccine Institute have provided some answers that could prove helpful as potential vaccines inch closer to testing.
The key to a specific maternal virus infecting the infant appears to be the virus’s ability to escape attack by antibodies in the mother’s blood, enabling transmission during pregnancy, delivery or breastfeeding. The findings were published March 29 in the journal PLOS Pathogens.
“This finding is important for vaccine development,” said senior author Sallie Permar, M.D., Ph.D., director of the Laboratory of Neonatal Viral Pathogen Immunity at the Duke Human Vaccine Institute. “We have shown that the ability of the mom’s antibodies to attack her own virus is an important contributor to the risk of mother-to-infant transmission, so we can now focus on using immune strategies to boost the responses against the mother’s virus.”
Permar and colleagues -- including lead author Amit Kumar and co-senior author Feng Gao, M.D., -- said establishing a definitive route of mother-to-child infection was a priority in light of transmissions that persist despite current therapies.
To eliminate the influence that anti-retroviral therapies might have on the mother’s virus, the research team used blood samples from 16 mothers and infant pairs enrolled in a study from the early 1990s, which pre-dated HIV therapy.
The researchers sequenced the viral genomes from the mothers and babies and found genetically diverse population of HIV in the pregnant women. Of those virus variants, the ones that were most resistant to the mothers’ antibodies were transmitted to their babies. That finding confirmed earlier research, which had not been definitive.
In a subsequent analysis, the researchers found that the transmitted viruses were also sensitive to broadly neutralizing antibodies, which are a focus of vaccine developers because they are effective against multiple strains of HIV.
“These findings suggest that there are alternative strategies we could pursue in addition to ART,” Kumar said. “As vaccines are developed, we could immunize the mother during pregnancy, which would enhance the mother’s immune response and lessen the likelihood of the baby being infected. This approach could augment ART and, we hope, end the pediatric HIV epidemic.”
In addition to Permar, Kumar and Gao, study authors include Claire E. P. Smith, Elena E. Giorgi, Joshua Eudailey, David R. Martinez, Karina Yusim, Ayooluwa O. Douglas, Lisa Stamper, Erin McGuire, Celia C. LaBranche, David C. Montefiori and Genevieve G. Fouda.
The study received funding from the National Institutes of Health (1R01AI22909).