Longitudinally Tracked, Rapid and Robust Antigen-Specific Germinal Center Responses in Non-Human Primates after a Single Nanoparticle Vaccine Immunization

Abstract

The first immunization in a protein prime-boost vaccination is likely to be a critical event for how the immune response unfolds. However, priming immunizations generally produce little circulating antibody (Ab) or T cell responses in blood and therefore have been poorly studied in large animal models and humans. Using fine needle aspirates (FNA) of draining lymph nodes (LN), we closely tracked the primary immune response in rhesus monkeys immunized intramuscularly (IM) or subcutaneously (SubQ) with eOD-GT8 60mer nanoparticle, an epitope-directed HIV Env CD4 binding site immunogen entering human clinical trial. Significant numbers of germinal center (GC) B cells and antigen-specific CD4 T cells were detectable in the draining LN as early as 7 days post-immunization and peaked at approximately day 21. Strikingly, SubQ immunization resulted in 10-fold larger antigen-specific BGC cell responses compared to IM immunization. Antibody responses were only modestly higher after SubQ immunization. Lymphatic drainage studies revealed that SubQ immunization at the deltoid results in faster, larger, and more consistent LN drainage than IM immunization, which paralleled results from drainage studies of upper leg LNs that indicated more efficient LN drainage after SubQ administration. Together, these data indicate that, in a large animal model, robust antigen-specific GC responses can occur rapidly to a single immunization with a nanoparticle immunogen and differential injection site drainage of a vaccine substantially impacts immune responses in local LNs.