Immune Profiles Identification by Vaccinomics After MVA Immunization in Randomized Clinical Study

随机临床研究中 MVA 免疫后通过疫苗组学鉴定免疫特征

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作者:Jorge Sanchez, Elena Gonçalves, Anuska Llano, Pedro Gonzáles, María Fernández-Maldonado, Annika Vogt, Angele Soria, Susana Perez, Samandhy Cedeño, Marco Antonio Fernández, Julien Nourikyan, Simon de Bernard, Carmela Ganoza, Eric Pedruzzi, Olivia Bonduelle, Beatriz Mothe, Carmen E Gòmez, Mariano Este

Background

Our previous work has demonstrated the benefits of transcutaneous immunization in targeting Langerhans cells and preferentially inducing CD8 T-cell responses.

Conclusion

Thus, vaccine delivery route perturbs early innate responses that shape the quality of adaptive immunity. Clinical

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.

Trial registration

http://ClinicalTrials.gov, identifier PER-073-13.

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