PedMAb advances long-acting antibody strategies for infant HIV prevention
Phase I/II study to determine Safety and Pharmacokinetics of subcutaneous administration of potent and broad anti-HIV-1 neutralising monoclonal antibodies (bNAb), given to HIV-1-exposed neonates and infants.
The PedMAb Consortium across Italy, France, Norway and South Africa delivered important clinical, scientific and capacity-building results to support the development of long-acting broadly neutralising antibodies (bNAbs) to eliminate vertical HIV transmission postnatally (through breastfeeding).
The consortium completed PedMAb1, a Phase 1 study evaluating the subcutaneous administration of bNAbs CAP256V2LS and VRC07-523LS to HIV-exposed infants born without HIV. The study demonstrated for the first time ever the safety of administering both bNAbs contemporaneously within 96 hours of birth and at three months of age.
PedMAb1 generated valuable pediatric pharmacokinetic data to inform antibody dosing, repeat administration and the design of future trials. The project established dried blood spot microsampling as a practical method for measuring antibody concentrations in infants, reducing the blood volume required and facilitating sample collection. Furthermore, the consortium developed laboratory methods to assess antibody activity in infants receiving antiretroviral prophylaxis.
Building on this experience, the consortium developed the PedMAb1-Ex study, using the promising long-acting bNAb ePGT121v1LS. Developed by the International AIDS Vaccine Initiative, ePGT121v1LS was selected due to its enhanced in vitro neutralising capabilities and safety in non-human primates. This phase 1 trial has started to administer ePGT121v1LS to adults not at risk of HIV acquisition, to establish the safety of intravenous, subcutaneous and intramuscular dosing. The pediatric phase 1 trial will start once adult safety is confirmed. It will explore the potential use of ePGT121v1LS as a novel intervention to prevent postnatal HIV transmission during periods of heightened vulnerability.
The knowledge, infrastructure and partnerships created by PedMAb provide a strong foundation for future studies aimed at eliminating postnatal HIV transmission.