9MSD

G002-293-0536 Fab in complex with 001428_T278M_L14 SOSIP and RM20A3 Fab

This is a non-PDB format compatible entry.

Summary for 9MSD

• Entry DOI: 10.2210/pdb9msd/pdb
• EMDB information: 48575
• Descriptor: 001428_T278M_L14 SOSIP gp140, G002-293-0536 Fab heavy chain, G002-293-0536 Fab light chain, ... (8 entities in total)
• Functional Keywords: g002, clinical trial, hiv-1, vrc01, human antibody, vaccine, env, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 15
• Total formula weight: 509483.33

Authors

Phulera, S.,Ozorowski, G.,Ward, A.B. (deposition date: 2025-01-09, release date: 2025-05-28)

Primary citation

Willis, J.R.,Prabhakaran, M.,Muthui, M.,Naidoo, A.,Sincomb, T.,Wu, W.,Cottrell, C.A.,Landais, E.,deCamp, A.C.,Keshavarzi, N.R.,Kalyuzhniy, O.,Lee, J.H.,Murungi, L.M.,Ogonda, W.A.,Yates, N.L.,Corcoran, M.M.,Phulera, S.,Musando, J.,Tsai, A.,Lemire, G.,Sein, Y.,Muteti, M.,Alamuri, P.,Bohl, J.A.,Holman, D.,Himansu, S.,Leav, B.,Reuter, C.,Lin, L.A.,Ding, B.,He, C.,Straus, W.L.,MacPhee, K.J.,Regadas, I.,Nyabundi, D.V.,Chirchir, R.,Anzala, A.,Kimotho, J.N.,Kibet, C.,Greene, K.,Gao, H.,Beatman, E.,Benson, K.,Laddy, D.,Brown, D.M.,Bronson, R.,Baptiste, J.,Gajjala, S.,Rikhtegaran-Tehrani, Z.,Benner, A.,Ramaswami, M.,Lu, D.,Alavi, N.,Amirzehni, S.,Kubitz, M.,Tingle, R.,Georgeson, E.,Phelps, N.,Adachi, Y.,Liguori, A.,Flynn, C.,McKenney, K.,Zhou, X.,Owuor, D.C.,Owuor, S.,Kim, S.Y.,Duff, M.,Kim, J.Y.,Gibson, G.,Baboo, S.,Diedrich, J.,Schiffner, T.,Shields, M.,Matsoso, M.,Santos, J.,Syvertsen, K.,Kennedy, A.,Schroeter, M.,Vekemans, J.,Yates, J.,Paulson, J.C.,Hyrien, O.,McDermott, A.B.,Maenetje, P.,Nyombayire, J.,Karita, E.,Ingabire, R.,Edward, V.,Muturi-Kioi, V.,Maenza, J.,Shapiro, A.E.,McElrath, M.J.,Edupuganti, S.,Taylor, B.S.,Diemert, D.,Ozorowski, G.,Koup, R.A.,Montefiori, D.,Ward, A.B.,Hedestam, G.K.,Tomaras, G.,Hunt, D.J.,Muema, D.,Sok, D.,Laufer, D.S.,Andrews, S.F.,Nduati, E.W.,Schief, W.R.
Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans.
Science, :eadr8382-eadr8382, 2025

PubMed Abstract: 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, 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 18% of IAVI-G002 participants experienced skin reactions. Priming induced bnAb precursors with substantial frequencies and SHM, and heterologous boosting elicited increased SHM, affinity, and neutralization activity toward bnAb development. 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.

PubMed: 40373112
DOI: 10.1126/science.adr8382

Experimental method

ELECTRON MICROSCOPY (3.2 Å)