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Human immunoglobulin gene allelic variation impacts germline-targeting vaccine priming.
deCamp, Allan C; Corcoran, Martin M; Fulp, William J; Willis, Jordan R; Cottrell, Christopher A; Bader, Daniel L V; Kalyuzhniy, Oleksandr; Leggat, David J; Cohen, Kristen W; Hyrien, Ollivier; Menis, Sergey; Finak, Greg; Ballweber-Fleming, Lamar; Srikanth, Abhinaya; Plyler, Jason R; Rahaman, Farhad; Lombardo, Angela; Philiponis, Vincent; Whaley, Rachael E; Seese, Aaron; Brand, Joshua; Ruppel, Alexis M; Hoyland, Wesley; Mahoney, Celia R; Cagigi, Alberto; Taylor, Alison; Brown, David M; Ambrozak, David R; Sincomb, Troy; Mullen, Tina-Marie; Maenza, Janine; Kolokythas, Orpheus; Khati, Nadia; Bethony, Jeffrey; Roederer, Mario; Diemert, David; Koup, Richard A; Laufer, Dagna S; McElrath, Juliana M; McDermott, Adrian B; Karlsson Hedestam, Gunilla B; Schief, William R.
Afiliação
  • deCamp AC; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA. adecamp@scharp.org.
  • Corcoran MM; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
  • Fulp WJ; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
  • Willis JR; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Cottrell CA; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Bader DLV; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Kalyuzhniy O; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Leggat DJ; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Cohen KW; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Hyrien O; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Menis S; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Finak G; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Ballweber-Fleming L; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Srikanth A; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Plyler JR; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Rahaman F; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Lombardo A; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
  • Philiponis V; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
  • Whaley RE; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Seese A; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Brand J; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Ruppel AM; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
  • Hoyland W; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
  • Mahoney CR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Cagigi A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Taylor A; IAVI, 125 Broad Street, 9th floor, New York, NY, 10004, USA.
  • Brown DM; IAVI, 125 Broad Street, 9th floor, New York, NY, 10004, USA.
  • Ambrozak DR; IAVI, 125 Broad Street, 9th floor, New York, NY, 10004, USA.
  • Sincomb T; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
  • Mullen TM; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
  • Maenza J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Kolokythas O; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Khati N; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Bethony J; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
  • Roederer M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Diemert D; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Koup RA; The Foundation for the National Institutes of Health, North Bethesda, MD, USA.
  • Laufer DS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • McElrath JM; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • McDermott AB; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Karlsson Hedestam GB; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Schief WR; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
NPJ Vaccines ; 9(1): 58, 2024 Mar 11.
Article em En | MEDLINE | ID: mdl-38467663
ABSTRACT
Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise for development of precision vaccines against major human pathogens. In a clinical trial of the eOD-GT8 60mer germline-targeting immunogen, higher frequencies of vaccine-induced VRC01-class bnAb-precursor B cells were observed in the high dose compared to the low dose group. Through immunoglobulin heavy chain variable (IGHV) genotyping, statistical modeling, quantification of IGHV1-2 allele usage and B cell frequencies in the naive repertoire for each trial participant, and antibody affinity analyses, we found that the difference between dose groups in VRC01-class response frequency was best explained by IGHV1-2 genotype rather than dose and was most likely due to differences in IGHV1-2 B cell frequencies for different genotypes. The results demonstrate the need to define population-level immunoglobulin allelic variations when designing germline-targeting immunogens and evaluating them in clinical trials.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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XML
PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article