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Publication Abstract from PubMed

Germline-targeting (GT) HIV vaccine strategies are predicated on deriving broadly neutralizing antibodies (bnAbs) through multiple boost immunogens. However, as the recruitment of memory B cells (MBCs) to germinal centers (GCs) is inefficient and may be derailed by serum antibody-induced epitope masking, driving further B cell receptor (BCR) modification in GC-experienced B cells after boosting poses a challenge. Using humanized immunoglobulin knockin mice, we found that GT protein trimer immunogen N332-GT5 could prime inferred-germline precursors to the V3-glycan-targeted bnAb BG18 and that B cells primed by N332-GT5 were effectively boosted by either of two novel protein immunogens designed to have minimum cross-reactivity with the off-target V1-binding responses. The delivery of the prime and boost immunogens as messenger RNA lipid nanoparticles (mRNA-LNPs) generated long-lasting GCs, somatic hypermutation, and affinity maturation and may be an effective tool in HIV vaccine development.

mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies.,Xie Z, Lin YC, Steichen JM, Ozorowski G, Kratochvil S, Ray R, Torres JL, Liguori A, Kalyuzhniy O, Wang X, Warner JE, Weldon SR, Dale GA, Kirsch KH, Nair U, Baboo S, Georgeson E, Adachi Y, Kubitz M, Jackson AM, Richey ST, Volk RM, Lee JH, Diedrich JK, Prum T, Falcone S, Himansu S, Carfi A, Yates JR 3rd, Paulson JC, Sok D, Ward AB, Schief WR, Batista FD Science. 2024 May 17;384(6697):eadk0582. doi: 10.1126/science.adk0582. Epub 2024 , May 17. PMID:38753770^[1]

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