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

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

2019

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

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