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Publication Abstract from PubMed

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.

Mutation-guided vaccine design: A process for developing boosting immunogens for HIV broadly neutralizing antibody induction.,Wiehe K, Saunders KO, Stalls V, Cain DW, Venkatayogi S, Martin Beem JS, Berry M, Evangelous T, Henderson R, Hora B, Xia SM, Jiang C, Newman A, Bowman C, Lu X, Bryan ME, Bal J, Sanzone A, Chen H, Eaton A, Tomai MA, Fox CB, Tam YK, Barbosa C, Bonsignori M, Muramatsu H, Alam SM, Montefiori DC, Williams WB, Pardi N, Tian M, Weissman D, Alt FW, Acharya P, Haynes BF Cell Host Microbe. 2024 May 8;32(5):693-709.e7. doi: 10.1016/j.chom.2024.04.006. , Epub 2024 Apr 25. PMID:38670093^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.