Abstract
Innate immunity modulates adaptive immunity and defines the magnitude, quality, and longevity of antigen-specific T- and B- cell immune memory. Various vaccine and administration factors influence the immune response to vaccination, including the route of vaccine delivery. We studied the dynamics of innate cell responses in blood using a preclinical model of non-human primates immunized with a live attenuated vaccinia virus, a recombinant Modified vaccinia virus Ankara (MVA) expressing a gag-pol-nef fusion of HIV-1, and mass cytometry. We previously showed that it induces a strong, early, and transient innate response, but also late phenotypic modifications of blood myeloid cells after two months when injected subcutaneously. Here, we show that the early innate effector cell responses and plasma inflammatory cytokine profiles differ between subcutaneous and intradermal vaccine injection. Additionally, we show that the intradermal administration fails to induce more highly activated/mature neutrophils long after immunization, in contrast to subcutaneous administration. Different batches of antibodies, staining protocols and generations of mass cytometers were used to generate the two datasets. Mass cytometry data were analyzed in parallel using the same analytical pipeline based on three successive clustering steps, including SPADE, and categorical heatmaps were compared using the Manhattan distance to measure the similarity between cell cluster phenotypes. Overall, we show that the vaccine per se is not sufficient for the late phenotypic modifications of innate myeloid cells, which are evocative of innate immune training. Its route of administration is also crucial, likely by influencing the early innate response, and systemic inflammation, and vaccine biodistribution.
Highlights
Like the antigen-specific antibody and Tcell responses, the early innate responses differ between subcutaneous (SC) and intradermal (ID) immunization, with the recruitment of distinct cell populations and activation of different immunomodulatory genes in skin and blood in response to a model live attenuated vaccine, Modified vaccinia virus Ankara (MVA), in non-human primates (NHPs) [8]
We assessed the humoral response to confirm the efficiency of vaccination, as Abs are the main immune correlate of protection for most vaccines [16], including vaccinia virus (VACV) and MVA against smallpox [17]
We focused the analysis on the granulocyte compartment, as our panel was solely dedicated to target innate myeloid cells, and because major phenotypic modifications occured mainly in granulocytes late after MVA SC immunizations [18]
Summary
Vaccination is among the major advances in terms of public health by conferring protection against many infectious diseases. The early innate immune response is among the first lines of antiviral defense and orchestrates and modulates the antigen-specific effector and memory B- and T-cell responses by determining the frequency, functions, and dynamics of antigenspecific T and B cells [2, 3].
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