Abstract
Vaccination is one of the most efficient public healthcare measures to fight infectious diseases. Nevertheless, the immune mechanisms induced in vivo by vaccination are still unclear. The route of administration, an important vaccination parameter, can substantially modify the quality of the response. How the route of administration affects the generation and profile of immune responses is of major interest. Here, we aimed to extensively characterize the profiles of the innate and adaptive response to vaccination induced after intradermal, subcutaneous, or intramuscular administration with a modified vaccinia virus Ankara model vaccine in non-human primates. The adaptive response following subcutaneous immunization was clearly different from that following intradermal or intramuscular immunization. The subcutaneous route induced a higher level of neutralizing antibodies than the intradermal and intramuscular vaccination routes. In contrast, polyfunctional CD8+ T-cell responses were preferentially induced after intradermal or intramuscular injection. We observed the same dichotomy when analyzing the early molecular and cellular immune events, highlighting the recruitment of cell populations, such as CD8+ T lymphocytes and myeloid-derived suppressive cells, and the activation of key immunomodulatory gene pathways. These results demonstrate that the quality of the vaccine response is shaped by early and subtle modifications of the innate immune response. In addition, the route of administration must be tailored to the desired type of protective immune response. This will be achieved through systems vaccinology and mathematical modeling, which will be critical for predicting the efficacy of the vaccination route for personalized medicine.
Highlights
Vaccination is one of the most effective public health approach to prevent infectious diseases
We combined a complete set of experimental data obtained by multiparameter techniques, at the cellular and molecular levels, with systems vaccinology approaches, providing a holistic view of the complex mechanisms of the vaccine response, to evaluate the impact of the administration route on the immune response
Modified Vaccinia virus Ankara (MVA) administration induced substantial myeloid cell recruitment, whereas B and T lymphocytes were reduced in the blood compartment
Summary
Vaccination is one of the most effective public health approach to prevent infectious diseases. For many vaccines, the mechanisms responsible for suitable immunity are still poorly understood. Vaccination routes are known to affect the quality of the vaccine response [1,2,3], the underlying molecular and cellular mechanisms at play at the injection site and in the draining lymphoid tissues are yet to be elucidated. The efficacy of the IM route requires a rapid diffusion of the vaccine antigens to draining lymph nodes [6]. Skin tissue contains a broad array of antigen-presenting cells (APCs), which are likely to affect the magnitude, duration, and orientation of antigenspecific immune memory, and represents a potentially superior vaccine delivery site despite receiving less attention than classical administration routes due to practicality [7]. Mohanan et al [11] showed that the administration route strongly influences the Th1 response, with higher IgG2a titers and IFNg production favored by the IM and ID routes over the SC route
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