8DTO

Vaccine elicited Antibody MU89 bound to CH848.D949.10.17_N133D_N138T.DS.SOSIP.664 HIV-1 Env trimer

Summary for 8DTO

• Entry DOI: 10.2210/pdb8dto/pdb
• EMDB information: 27706
• Descriptor: CH848.3.D0949.10.17chim.6R.DS.SOSIP.664_N133D_N138T gp120, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• Functional Keywords: hiv-1 envelope, vaccine-induced antibody, broadly neutralizing antibody, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 12
• Total formula weight: 317743.39

Authors

Stalls, V.,Acharya, P. (deposition date: 2022-07-26, release date: 2023-04-19, Last modification date: 2024-10-16)

Primary citation

Wiehe, K.,Saunders, K.O.,Stalls, V.,Cain, D.W.,Venkatayogi, S.,Martin Beem, J.S.,Berry, M.,Evangelous, T.,Henderson, R.,Hora, B.,Xia, S.M.,Jiang, C.,Newman, A.,Bowman, C.,Lu, X.,Bryan, M.E.,Bal, J.,Sanzone, A.,Chen, H.,Eaton, A.,Tomai, M.A.,Fox, C.B.,Tam, Y.K.,Barbosa, C.,Bonsignori, M.,Muramatsu, H.,Alam, S.M.,Montefiori, D.C.,Williams, W.B.,Pardi, N.,Tian, M.,Weissman, D.,Alt, F.W.,Acharya, P.,Haynes, B.F.
Mutation-guided vaccine design: A process for developing boosting immunogens for HIV broadly neutralizing antibody induction.
Cell Host Microbe, 32:693-709.e7, 2024

PubMed Abstract: A major goal of HIV-1 vaccine development is the induction of broadly neutralizing antibodies (bnAbs). Although success has been achieved in initiating bnAb B cell lineages, design of boosting immunogens that select for bnAb B cell receptors with improbable mutations required for bnAb affinity maturation remains difficult. Here, we demonstrate a process for designing boosting immunogens for a V3-glycan bnAb B cell lineage. The immunogens induced affinity-matured antibodies by selecting for functional improbable mutations in bnAb precursor knockin mice. Moreover, we show similar success in prime and boosting with nucleoside-modified mRNA-encoded HIV-1 envelope trimer immunogens, with improved selection by mRNA immunogens of improbable mutations required for bnAb binding to key envelope glycans. These results demonstrate the ability of both protein and mRNA prime-boost immunogens for selection of rare B cell lineage intermediates with neutralizing breadth after bnAb precursor expansion, a key proof of concept and milestone toward development of an HIV-1 vaccine.

PubMed: 38670093
DOI: 10.1016/j.chom.2024.04.006

Experimental method

ELECTRON MICROSCOPY (3.57 Å)