Abstract
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-1β) 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.
Highlights
Vaccination is one of the most important achievements made in the field of public health[1,2]
We reported late changes in the phenotype of innate myeloid cells in the blood, including neutrophils, monocytes, classical dendritic cells[15], and NK cells[16], which occurred between 2 weeks and 2 months after the first immunization
We demonstrate here that shortening to 2 weeks the time-interval between modified vaccinia virus Ankara (MVA) injections resulted in an impaired secondary Ab responses, and similar innate responses to both immunizations
Summary
Vaccination is one of the most important achievements made in the field of public health[1,2]. Many vaccine-induced mechanisms are still unknown, limiting the design of vaccine immunogens and strategies, in particular for diseases such as AIDS, tuberculosis and malaria. Most vaccines require multiple injections to achieve a significant level of population (herd immunity) and individual immune protection[3,4,5]. The optimization of vaccine responses certainly requires a better understanding of how the time-interval between immunizations affects the molecular and cellular mechanisms inducing immune memory. The modified vaccinia virus Ankara (MVA), a highly attenuated third-generation vaccinia-based smallpox vaccine, is a relevant vaccine model, as it induces both strong humoral and cellular immunity[8]. In contrast to vaccinia virus (VACV), from which it is derived and which provides life-long protection after a single administration, preclinical studies have shown that MVA requires a booster immunization to induce protective immunity[8]. We need to increase our knowledge of its mode of action
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