Journal
NPJ VACCINES
Volume 5, Issue 1, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41541-020-0175-8
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Funding
- Investissements d'Avenir programs [ANR-10-LABX-77-01]
- Vaccine Research Institute (VRI), Creteil (ImMemory research program) [ANR-11-INBS-0008]
- Infectious Disease Models and Innovative Therapies (IDMIT, Fontenay-aux-Roses, France) infrastructure
- FlowCyTech facility (IDMIT, Fontenay-aux-Roses, France)
- European Union, EVHA H2020 project [681032]
- European Union, TRANSVAC2 H2020 [730964]
- ANRS (France Recherche Nord & Sud Sida-HIV Hepatites)
- [ANR-10-EQPX-02-01]
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Comprehending the mechanisms behind the impact of vaccine regimens on immunity is critical for improving vaccines. Indeed, the time-interval between immunizations may influence B and T cells, as well as innate responses. We compared two vaccine schedules using cynomolgus macaques immunized with an attenuated vaccinia virus. Two subcutaneous injections 2 weeks apart led to an impaired secondary antibody response and similar innate myeloid responses to both immunizations. In contrast, a delayed boost (2 months) improved the quality of the antibody response and involved more activated/mature innate cells, induced late after the prime and responding to the recall. The magnitude and quality of the secondary antibody response correlated with the abundance of these neutrophils, monocytes, and dendritic cells that were modified phenotypically and enriched prior to revaccination at 2 months, but not 2 weeks. These late phenotypic modifications were associated with an enhanced ex vivo cytokine production (including IL-12/23 and IL-1 beta) by PBMCs short after the second immunization, linking phenotype and functions. This integrated analysis reveals a deep impact of the timing between immunizations, and highlights the importance of early but also late innate responses involving phenotypical changes, in shaping humoral immunity.
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