Focusing antibody responses to the fusion peptide in rhesus macaques.

Journal

bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187

Informations de publication

Date de publication:
27 Jun 2023
Historique:
pubmed: 10 7 2023
medline: 10 7 2023
entrez: 10 7 2023
Statut: epublish

Résumé

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 elicit immune responses against the conserved fusion peptide. Antibody specificities and GC responses were tracked longitudinally using electron microscopy polyclonal epitope mapping (EMPEM) and lymph node fine-needle aspirates, respectively. Application of cryoEMPEM delineated key residues for on-target and off-target responses that can drive the next round of structure-based vaccine design.

Identifiants

DOI: 10.1101/2023.06.26.545779 PMID: 37425865 PMC: PMC10327030
pubmed: 37425865
doi: 10.1101/2023.06.26.545779
pmc: PMC10327030
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NIAID NIH HHS
ID : UM1 AI144462
Pays : United States
Organisme : Bill & Melinda Gates Foundation
ID : INV-007368
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI048240
Pays : United States
Organisme : NIGMS NIH HHS
ID : U24 GM129547
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI145629
Pays : United States
Organisme : NIH HHS
ID : P51 OD011132
Pays : United States

Déclaration de conflit d'intérêts

Conflicts of Interest None.

Auteurs

Christopher A Cottrell (CA)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.

Payal P Pratap (PP)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.

Kimberly M Cirelli (KM)

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.

Diane G Carnathan (DG)

International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium 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.

Chiamaka A Enemuo (CA)

Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.

Aleksandar Antanasijevic (A)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.

Gabriel Ozorowski (G)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.

Leigh M Sewall (LM)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.

Hongmei Gao (H)

Duke Human Vaccine Institute and Department of Surgery, Duke University Medical Center, Durham, NC, USA.

Kelli M Greene (KM)

Duke Human Vaccine Institute and Department of Surgery, Duke University Medical Center, Durham, NC, USA.

Joel D Allen (JD)

School of Biological Sciences, University of Southampton, Southampton, SO17 1BJ, UK.

Julia T Ngo (JT)

Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.

Yury Choe (Y)

Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.

Bartek Nogal (B)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.

Murillo Silva (M)

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Jinal Bhiman (J)

Centre for HIV and STI, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.

Matthias Pauthner (M)

Ragon Institute of MGH, MIT and Harvard, Cambridge, MA02139, USA.

Darrell J Irvine (DJ)

International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium 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.

David Montefiori (D)

Duke Human Vaccine Institute and Department of Surgery, Duke University Medical Center, Durham, NC, USA.

Max Crispin (M)

School of Biological Sciences, University of Southampton, Southampton, SO17 1BJ, UK.

Dennis R Burton (DR)

International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium 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, California, USA.
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA02139, USA.

Guido Silvestri (G)

International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium 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.

Shane Crotty (S)

International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Center for Infectious Disease and Vaccine Research, 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, California, USA.

Andrew B Ward (AB)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.

Classifications MeSH