Rapid Germinal Center and Antibody Responses in Non-human Primates after a Single Nanoparticle Vaccine Immunization
Open accessAbstract
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.
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Germinal centre responses induced by more robust adjuvants such as sheep red blood cells, complete Freund's adjuvant or saponin-based adjuvants tend to peak at 2-4 weeks after vaccination and can persist at low frequencies for several months.
“Germinal centre responses induced by immunization with more robust adjuvants such as sheep red blood cells, complete Freund’s adjuvant or saponin-based adjuvants tend to peak slightly later, at 2–4 weeks after vaccination, and can persist at low frequencies for several months27–33.”
From SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses (2021) · cites this paper as [32]
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A Broad Survey and Functional Analysis of Immunoglobulin Loci Variation in Rhesus MacaquesPreprint
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Dendritic Cell Organization and Function in Innate and Adaptive Immune Defense Within Lymph Nodes
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Neonatal SHIV infection in rhesus macaques elicited heterologous HIV-1-neutralizing antibodies
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A Polylactide-Based Micellar Adjuvant Improves the Intensity and Quality of Immune Response
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Recent advances in development of nano-carriers for immunogene therapy in various complex disorders.
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Comparison of fine‐needle aspiration techniques
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Characterization of Turbo, a TLR Ligand-based Adjuvant for Glycoconjugate Vaccines
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Self-citation
- Authors
- Havenar-Daughton, C., Carnathan, D. G., Boopathy, A. V., Upadhyay, A. A., Murrell, B., Reiss, S. M., Enemuo, C. A., Gebru, E. H., Choe, Y., Dhadvai, P., Viviano, F., Kaushik, K., Bhiman, J. N., Briney, B., Burton, D. R., Bosinger, S. E., Schief, W. R., Irvine, D. J., Silvestri, G., & Crotty, S.
- Affiliations
- Scripps Research Institute (US)
- Koch Institute for Integrative Cancer Research At MIT (US)
- Emory University (US)
- Karolinska Institutet (SE)
- Corresponding author
- Silvestri, Guido
- Crotty, Shane
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2019-11
- Volume
- 29
- Issue
- 7
- Pages
- 1756-1766.e8
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6905039
- OpenAlex
- W2988849718
- Cited by
- 58
- References
- 43
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 5 · 2023: 13 · 2022: 9 · 2021: 11 · 2020: 12
- FWCI
- 3.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- nanoparticle vaccine, Plasmodium falciparum, rhesus monkeys, germinal center B cells, antibody kinetics, subcutaneous immunization, intramuscular vaccination, lymph node drainage, axillary lymph nodes, antigen-specific CD4+ T cells, vaccine immunogenicity
- MeSH terms
- Animals, Antibody Formation, B-Lymphocytes, Humans, Immunization, Macaca mulatta, Male, Vaccines, CD4-Positive T-Lymphocytes, Germinal Center, Biopsy, Fine-Needle, Nanoparticles
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