Two-dose priming immunization amplifies humoral immunity by synchronizing vaccine delivery with the germinal center response
Prolonging exposure to subunit vaccines during the primary immune response enhances humoral immunity. Escalating-dose immunization (EDI), administering vaccines every other day in an increasing pattern over 2 weeks, is particularly effective but challenging to implement clinically. Here, using an HIV Env trimer/saponin adjuvant vaccine, we explored simplified EDI regimens and found that a two-shot regimen administering 20% of the vaccine followed by the remaining 80% of the dose 7 days later increased T<sub>FH</sub> responses 6-fold, antigen-specific germinal center (GC) B cells 10-fold, and serum antibody titers 10-fold compared with bolus immunization. Computational modeling of T<sub>FH</sub> priming and the GC response suggested that enhanced activation/antigen loading on dendritic cells and increased capture of antigen delivered in the second dose by follicular dendritic cells contribute to these effects, predictions we verified experimentally. These results suggest that a two-shot priming approach can be used to substantially enhance responses to subunit vaccines.
Authors
- Sachin Bhagchandani (ORCID: https://orcid.org/0000-0003-4410-5800)
- Anna Romanov (ORCID: https://orcid.org/0000-0002-1239-4946)
- Laura Maiorino (ORCID: https://orcid.org/0000-0001-8217-1337)
- Aereas Aung (ORCID: https://orcid.org/0000-0003-2429-5547)
- Heikyung Suh (ORCID: https://orcid.org/0000-0003-0787-298X)
- Shengwei Wu (ORCID: https://orcid.org/0000-0001-8175-3490)
- Arup K. Chakraborty (ORCID: https://orcid.org/0000-0003-1268-9602)
- Kristen A. Rodrigues (ORCID: https://orcid.org/0000-0002-0680-9834)
- Elana Ben‐Akiva (ORCID: https://orcid.org/0000-0003-1085-5902)
- Leerang Yang (ORCID: https://orcid.org/0000-0002-7819-4381)
- Jonathan Lam (ORCID: https://orcid.org/0000-0002-2811-7177)
- Darrell J. Irvine (ORCID: https://orcid.org/0000-0002-8637-1405)
- Anika Wadhera (ORCID: https://orcid.org/0009-0009-4694-6129)
Institutions
- Howard Hughes Medical Institute (US)
- Ragon Institute of MGH, MIT and Harvard (US)
- Massachusetts Institute of Technology (US)
Publication Details
- Journal
- Science Immunology
- Published
- 2024-09-20
- DOI
- https://doi.org/10.1126/sciimmunol.adl3755
- Citations
- 19
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 4.57
Funders
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
- National Institutes of Health
- National Cancer Institute