Rapid Germinal Center and Antibody Responses in Non-human Primates after a Single Nanoparticle Vaccine Immunization

Colin Havenar-Daughton; Diane G. Carnathan; Archana V. Boopathy; Amit A. Upadhyay; Ben Murrell; Samantha M. Reiss; Chiamaka A. Enemuo; Etse H. Gebru; Yury Choe; Pallavi Dhadvai; Federico Viviano; Kirti Kaushik; Jinal N. Bhiman; Bryan Briney; Dennis R. Burton; Steven E. Bosinger; William R. Schief; Darrell J. Irvine; Guido Silvestri; Shane Crotty

Cell Reports (Nov 2019)

Rapid Germinal Center and Antibody Responses in Non-human Primates after a Single Nanoparticle Vaccine Immunization

Colin Havenar-Daughton,
Diane G. Carnathan,
Archana V. Boopathy,
Amit A. Upadhyay,
Ben Murrell,
Samantha M. Reiss,
Chiamaka A. Enemuo,
Etse H. Gebru,
Yury Choe,
Pallavi Dhadvai,
Federico Viviano,
Kirti Kaushik,
Jinal N. Bhiman,
Bryan Briney,
Dennis R. Burton,
Steven E. Bosinger,
William R. Schief,
Darrell J. Irvine,
Guido Silvestri,
Shane Crotty

Affiliations

Colin Havenar-Daughton: Division of Vaccine Discovery, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA
Diane G. Carnathan: Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA
Archana V. Boopathy: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Amit A. Upadhyay: Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA
Ben Murrell: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 17177, Sweden
Samantha M. Reiss: Division of Vaccine Discovery, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA
Chiamaka A. Enemuo: Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA
Etse H. Gebru: Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA
Yury Choe: Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA
Pallavi Dhadvai: Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA
Federico Viviano: Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA
Kirti Kaushik: Division of Vaccine Discovery, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA
Jinal N. Bhiman: Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA
Bryan Briney: Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA
Dennis R. Burton: Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA
Steven E. Bosinger: Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA
William R. Schief: Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA
Darrell J. Irvine: Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA
Guido Silvestri: Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Corresponding author
Shane Crotty: Division of Vaccine Discovery, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, San Diego, CA 92103, USA; Corresponding author

Journal volume & issue: Vol. 29, no. 7
pp. 1756 – 1766.e8

Abstract

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Summary: The first immunization in a protein prime-boost vaccination is likely to be critical for how the immune response unfolds. Using fine needle aspirates (FNAs) of draining lymph nodes (LNs), we tracked the kinetics of the primary immune response in rhesus monkeys immunized intramuscularly (IM) or subcutaneously (s.c.) with an eOD-GT8 60-mer nanoparticle immunogen to facilitate clinical trial design. Significant numbers of germinal center B (BGC) cells and antigen-specific CD4 T cells were detectable in the draining LN as early as 7 days post-immunization and peaked near day 21. Strikingly, s.c. immunization results in 10-fold larger antigen-specific BGC cell responses compared to IM immunization. Lymphatic drainage studies revealed that s.c. immunization resulted in faster and more consistent axillary LN drainage than IM immunization. These data indicate robust antigen-specific germinal center responses can occur rapidly to a single immunization with a nanoparticle immunogen and vaccine drainage substantially impacts immune responses in local LNs. : The first immunization of protein prime-boost vaccination is likely critical but has been understudied in large animals and humans. Havenar-Daughton et al. use lymph node fine needle aspirates to determine primary germinal center response kinetics in rhesus monkeys immunized intramuscularly or subcutaneously with a clinical trial candidate nanoparticle immunogen. Keywords: HIV, antibodies, T follicular helper cells

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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