Immune Profiles Identification by Vaccinomics After MVA Immunization in Randomized Clinical Study
© 2020 Sanchez, Gonçalves, Llano, Gonzáles, Fernández-Maldonado, Vogt, Soria, Perez, Cedeño, Fernández, Nourikyan, de Bernard, Ganoza, Pedruzzi, Bonduelle, Mothe, Gòmez, Esteban, Garcia, Lama, Brander and Combadiere. ; [Background]: Our previous work has demonstrated the benefits of transcutaneous immunization in targeting Langerhans cells and preferentially inducing CD8 T-cell responses. ; [Methods]: In this randomized phase Ib clinical trial including 20 HIV uninfected volunteers, we compared the safety and immunogenicity of the MVA recombinant vaccine expressing HIV-B antigen (MVA-B) by transcutaneous and intramuscular routes. We hypothesized that the quality of innate and adaptive immunity differs according to the route of immunization and explored the quality of the vector vaccine-induced immune responses. We also investigated the early blood transcriptome and serum cytokine levels to identify innate events correlated with the strength and quality of adaptive immunity. ; [Results]: We demonstrate that MVA-B vaccine is safe by both routes, but that the quality and intensity of both innate and adaptive immunity differ significantly. Transcutaneous vaccination promoted CD8 responses in the absence of antibodies and slightly affected gene expression, involving mainly genes associated with metabolic pathways. Intramuscular vaccination, on the other hand, drove robust changes in the expression of genes involved in IL-6 and interferon signalling pathways, mainly those associated with humoral responses, and also some levels of CD8 response. ; [Conclusion]: Thus, vaccine delivery route perturbs early innate responses that shape the quality of adaptive immunity. ; This project has received funding from the European Union's Seventh Programme for research, technological development and demonstration under grant agreement No 241904, the European Union's Horizon 2020 Research, Innovation Programme under grant agreement No. 681137, NIH grant P01-AI131568 and La Fondation pour la Recherche Medicale.