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

doi:10.1016/j.celrep.2019.10.008

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

Cell Rep. 2019 Nov 12;29(7):1756-1766.e8. doi: 10.1016/j.celrep.2019.10.008.

Authors

Colin Havenar-Daughton¹, Diane G Carnathan², Archana V Boopathy³, Amit A Upadhyay⁴, Ben Murrell⁵, Samantha M Reiss¹, Chiamaka A Enemuo⁴, Etse H Gebru⁴, Yury Choe⁴, Pallavi Dhadvai⁴, Federico Viviano⁴, Kirti Kaushik¹, Jinal N Bhiman⁶, Bryan Briney⁷, Dennis R Burton⁶, Steven E Bosinger⁴, William R Schief⁶, Darrell J Irvine⁸, Guido Silvestri⁹, Shane Crotty¹⁰

Affiliations

¹ 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.
² 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.
³ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁴ 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.
⁵ Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 17177, Sweden.
⁶ 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.
⁷ 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.
⁸ 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.
⁹ 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. Electronic address: gsilves@emory.edu.
¹⁰ 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. Electronic address: shane@lji.org.

Abstract

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 (B_GC) 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 B_GC 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.

Keywords: HIV; T follicular helper cells; antibodies.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Antibody Formation*
B-Lymphocytes / immunology*
B-Lymphocytes / pathology
Biopsy, Fine-Needle
CD4-Positive T-Lymphocytes / immunology*
CD4-Positive T-Lymphocytes / pathology
Germinal Center / immunology*
Germinal Center / pathology
Humans
Immunization*
Macaca mulatta
Male
Nanoparticles*
Vaccines / immunology
Vaccines / pharmacology*

Substances

Vaccines

Abstract

Publication types

MeSH terms

Substances

Grants and funding