Abstract Body

Background:

Over 150,000 children are infected with HIV-1 every year. Despite increased availability and access to antiretroviral therapy (ART), up to 5% of women with HIV still transmit the virus to their infants. While development of broadly neutralizing antibodies (bNAbs) through vaccination and therapeutic interventions are intended to prevent mother-to-child-transmission of HIV-1, recent evidence suggests that there may be limitations to bNAb-based approaches. Our group has demonstrated viral escape of variants in the presence of maternal plasma bNAbs targeting the V3 glycan site and a dominant bnAb specificity in postnatal transmitting women plasma. Thus, we hypothesize that HIV-infected women with bNAbs targeting a single epitope may be at high risk of viral escape that can lead to vertical transmission.

Methods:

We acquired plasma from 15 perinatal transmitting women with HIV from the US-based, pre-ART era Mother-Infant Cohort Study (MICS). Plasma was collected at delivery and assessed for neutralization activity against a global HIV-1 panel. Additionally, we screened postnatal HIV-transmitting women from the Breastfeeding, Antiretroviral, and Nutrition Study (BAN) and Center for HIV/AIDS Vaccine Immunology 009 (CHAVI009) for plasma neutralizing activity (BAN: n = 21 and CHAVI009: n = 3 postnatal HIV-transmitting women). MICS and CHAVI samples were also screened against murine leukemia virus (MLV) and BAN samples against Vesicular Stomatitis Virus-G (VSV-G) for non-specific neutralization.

Results:

Six out of 15 (40%) perinatal HIV-transmitting women from the MICS cohort neutralized over 50% of viruses of a heterologous, 10-virus global panel after correcting for non-specific neutralization activity (MLV). While this rate is higher than that reported in HIV-infected adults (20-30%), high neutralization breadth was also found among postnatal transmitting women with HIV in the BAN and CHAVI cohorts (18 of 24, 75%) indicating that transmission during perinatal and postnatal settings may involve a similar high rate of maternal bnAb responses that could lead to viral escape.

Conclusions:

The finding of high plasma bnAb rates in perinatal HIV-transmitted, ART-untreated women is similar to that observed for postnatal HIV-transmitting women and might indicate role for viral escape of neutralization in perinatal transmission. Immune interventions involving multispecific bNAbs that are synergistic with ART may be key for bnAb-based strategies for ending the pediatric HIV epidemic.