Priming antibody responses to the fusion peptide in rhesus macaques.

Autor: Cottrell CA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.; Center for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA., Pratap PP; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.; Center for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA., Cirelli KM; Center for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA.; La Jolla Institute for Immunology, La Jolla, CA, 92037, USA., Carnathan DG; Center for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA.; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, 30329, USA., Enemuo CA; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, 30329, USA., Antanasijevic A; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.; Center for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA., Ozorowski G; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.; Center for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA., Sewall LM; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.; Center for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA., Gao H; Duke Human Vaccine Institute and Department of Surgery, Duke University Medical Center Durham, Durham, NC, USA., Allen JD; School of Biological Sciences, University of Southampton, Southampton, SO17 1BJ, UK., Nogal B; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.; Center for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA., Silva M; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA., Bhiman J; Center for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA.; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA., Pauthner M; Center for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA.; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA., Irvine DJ; Center for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA., Montefiori D; Duke Human Vaccine Institute and Department of Surgery, Duke University Medical Center Durham, Durham, NC, USA., Crispin M; Center for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA.; School of Biological Sciences, University of Southampton, Southampton, SO17 1BJ, UK., Burton DR; Center for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA.; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA., Silvestri G; Center for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA.; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, 30329, USA., Crotty S; Center for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA.; La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.; Division of Infectious Disease and Global Public Health, Department of Medicine, University of California, San Diego, La Jolla, CA, USA., Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA. andrew@scripps.edu.; Center for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA. andrew@scripps.edu.
Jazyk: angličtina
Zdroj: NPJ vaccines [NPJ Vaccines] 2024 Jul 12; Vol. 9 (1), pp. 126. Date of Electronic Publication: 2024 Jul 12.
DOI: 10.1038/s41541-024-00918-9
Abstrakt: Immunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an effective HIV vaccine. Rational protein vaccine design and non-conventional immunization strategies are potential avenues to overcome these hurdles. Here, we report using implantable osmotic pumps to continuously deliver a series of epitope-targeted immunogens to rhesus macaques over the course of six months to prime and elicit antibody responses against the conserved fusion peptide (FP). GC responses and antibody specificities were tracked longitudinally using lymph node fine-needle aspirates and electron microscopy polyclonal epitope mapping (EMPEM), respectively, to show antibody responses to the FP/N611 glycan hole region were primed, although exhibited limited neutralization breadth. Application of cryoEMPEM delineated key residues for on-target and off-target responses that can drive the next round of structure-based vaccine design.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: