PedMAb: on your marks, get set, go!
Breastmilk optimises child survival in low- and middle income high HIV prevalence settings. However, breastmilk transmission of HIV continues to contribute to residual HIV mother-to-child transmission (MCTC). PedMAb’s aim is to ensure the development of a promising HIV-MTCT prevention strategy with broad anti-HIV-1 neutralizing monoclonal antibodies (bNAbs). The main objective is to complete two clinical trials, to define the optimal dose(s), timing, and the ideal combination(s) of bNAbs administered to breastfeeding HIV exposed uninfected neonates and infants born to HIV-infected women.
The long-acting (LS) version of the bNAbs CAP256, never tested in pediatric populations, and VRC07-523, were chosen for their characteristics. They target different viral regions involved in cell entry – the V1/V2 glycan region (CAP256V2LS) and CD4-binding site (VRC07-523LS) of the HIV envelope; they have neutralization breadth for HIV subtype C (dominant in South Africa) and other subtypes to cover also viruses circulating in other high prevalent areas beside South Africa; and their potency and availability of the formulation for subcutaneous administration, which in children is preferable to intravenous administration.
The PedMAb consortium held their second annual meeting in Durban, South Africa on 13-14 April 2023. Day 1 took place at the South African Medical Research Council and day 2 at the MRC Chatsworth clinical research site located within the premises of the R.K. Khan Hospital. The meeting brought together the entire PedMAb consortium, from Milan, Italy; Montpellier, France; Bergen, Norway and South Africa. Partners reviewed trial progress and further developed technical approaches. Thus far, arm 1 with the low dose of CAP256V2LS (5 mg/kg) is fully enrolled with eight neonates. All have completed the 6 months follow-up visits with 100% retention. Currently randomised recruitment is completed for arms 2 (CAP256V2LS at 10 mg/kg) and 4 (VRC07-523LS at 20 mg/ml). Safety data has been reviewed two-weekly and all adverse events have not been related to the study product. PK data are currently being analysed.