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mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies.
Xie, Zhenfei; Lin, Ying-Cing; Steichen, Jon M; Ozorowski, Gabriel; Kratochvil, Sven; Ray, Rashmi; Torres, Jonathan L; Liguori, Alessia; Kalyuzhniy, Oleksandr; Wang, Xuesong; Warner, John E; Weldon, Stephanie R; Dale, Gordon A; Kirsch, Kathrin H; Nair, Usha; Baboo, Sabyasachi; Georgeson, Erik; Adachi, Yumiko; Kubitz, Michael; Jackson, Abigail M; Richey, Sara T; Volk, Reid M; Lee, Jeong Hyun; Diedrich, Jolene K; Prum, Thavaleak; Falcone, Samantha; Himansu, Sunny; Carfi, Andrea; Yates, John R; Paulson, James C; Sok, Devin; Ward, Andrew B; Schief, William R; Batista, Facundo D.
Afiliação
  • Xie Z; The Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Lin YC; The Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Steichen JM; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Ozorowski G; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Kratochvil S; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Ray R; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Torres JL; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Liguori A; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Kalyuzhniy O; The Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Wang X; The Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Warner JE; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Weldon SR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Dale GA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Kirsch KH; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Nair U; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Baboo S; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Georgeson E; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Adachi Y; The Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Kubitz M; The Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Jackson AM; The Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Richey ST; The Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Volk RM; The Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Lee JH; The Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Diedrich JK; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Prum T; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Falcone S; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Himansu S; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Carfi A; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Yates JR; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Paulson JC; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Sok D; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Ward AB; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Schief WR; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Batista FD; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Science ; 384(6697): eadk0582, 2024 May 17.
Article em En | MEDLINE | ID: mdl-38753770
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Anticorpos Anti-HIV / HIV-1 / Imunização Secundária / Vacinas contra a AIDS / Centro Germinativo / Nanopartículas / Anticorpos Amplamente Neutralizantes / Vacinas de mRNA Limite: Animals / Female / Humans Idioma: En Revista: Science Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Anticorpos Anti-HIV / HIV-1 / Imunização Secundária / Vacinas contra a AIDS / Centro Germinativo / Nanopartículas / Anticorpos Amplamente Neutralizantes / Vacinas de mRNA Limite: Animals / Female / Humans Idioma: En Revista: Science Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos