Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans
- Jordan R. Willis
- Madhu Prabhakaran
- Michelle Muthui
- Ansuya Naidoo
- Troy Sincomb
- Weiwei Wu
- Christopher A. Cottrell
- Elise Landais
- Allan C. deCamp
- Nahid R. Keshavarzi
- Oleksandr Kalyuzhniy
- Jeong Hyun Lee
- Linda M. Murungi
- Wilfrida A. Ogonda
- Nicole L. Yates
- Martin M. Corcoran
- Swastik Phulera
- Joel Musando
- Amanda Tsai
- Gabrielle Lemire
- Yiakon Sein
- Michael Muteti
- Praveen Alamuri
- Jennifer A. Bohl
- Drienna Holman
- Sunny Himansu
- Brett Leav
- Caroline Reuter
- Li-An Lin
- Baoyu Ding
- Chunla He
- Walter L. Straus
- Kellie J. MacPhee
- Isabel Regadas
- Diana V. Nyabundi
- Ruth Chirchir
- Omu Anzala
- John N. Kimotho
- Caleb Kibet
- Kelli Greene
- Hongmei Gao
- Erica Beatman
- Kiara Benson
- Dominick Laddy
- David M. Brown
- Rhianna Bronson
- Jalen Jean-Baptiste
- Suprabhath Gajjala
- Zahra Rikhtegaran Tehrani
- Alison Benner
2025-05-15
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 substantial frequencies and SHM; heterologous boosting elicited increased SHM, affinity, and neutralization activity toward bnAb development; and elicited antibodies exhibited precise bnAb structural mimicry. The results establish clinical proof of concept that heterologous boosting can advance bnAb precursor maturation and demonstrate bnAb priming in Africa, where the HIV burden is highest.