Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans

A leading HIV vaccine strategy requires a priming immunogen to induce broadly neutralizing antibody (bnAb) precursors, followed by a series of heterologous boosters to elicit somatic hypermutation (SHM) and produce bnAbs. In two randomized, open-label phase 1 human clinical trials, IAVI G002 in the United States and IAVI G003 in Rwanda and South Africa (IAVI, International Aids Vaccine Initiative), we evaluated the safety and immunogenicity of mRNA-encoded nanoparticles as priming immunogens (both trials) and first-boosting immunogens (IAVI G002). The vaccines were generally safe and well tolerated, except that 18% of IAVI G002 participants experienced skin reactions. Priming induced bnAb precursors with…