9MSY

G002-480-0546 Fab in complex with V703-0537_T278M_L14 SOSIP and BG18 Fab

Summary for 9MSY

• Entry DOI: 10.2210/pdb9msy/pdb
• EMDB information: 48591
• Descriptor: V703-0537_T278M_L14 SOSIP, 2-acetamido-2-deoxy-beta-D-glucopyranose, BG18 Fab heavy chain, ... (10 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: 522820.68

Authors

Phulera, S.,Ozorowski, G.,Ward, A.B. (deposition date: 2025-01-10, release date: 2025-05-28, Last modification date: 2025-08-13)

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, O.,Kimotho, J.N.,Kibet, C.,Greene, K.,Gao, H.,Beatman, E.,Benson, K.,Laddy, D.,Brown, D.M.,Bronson, R.,Jean-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.A.,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 3rd, J.R.,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.,Karlsson Hedestam, G.B.,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, 389: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 (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.

PubMed: 40373112
DOI: 10.1126/science.adr8382

Experimental method

ELECTRON MICROSCOPY (3.4 Å)