Snowbird Resort, Snowbird, UT, United States COVID-19 vaccine, Innate immune response, mRNA vaccination, SARS-CoV-2 https://phaidrabg.bg.ac.rs/o:36555 info:eu-repo/semantics/conferenceProceedings Jacobi, Ronald Cvetković, Jelena Beckers, Lisa Miranda-Bedate, Alberto Wijmenga Monsuur, Alienke Pinelli, Elena Boer, Mardi van de Garde, Martijn http://creativecommons.org/licenses/by-nc-nd/4.0/legalcode eng Innate and adaptive immune responses after primary COVID-19 mRNA vaccination: in the search for surrogates of vaccine-induced protection startpage: 49 endpage: 30 Despite the effective vaccine strategies to combat COVID-19, new SARS-CoV-2 strains emerge and vaccine-induced immunity wanes with consequential breakthrough infections. Therefore, a better understanding of the mechanisms that determine the quality and quantity of underlining immune protection by the COVID-19 vaccines is crucial. The vaccine induced innate immune response, that shape the protective adaptive responses, could be used as surrogate of vaccine-induced protective responses and help to identify individuals with supra- or sub-optimal responses. Here we characterized the innate immune responses of adults, 1 to 3 days after receiving a primary COVID-19 mRNA vaccination, which will be correlated with adaptive outcome. In the IIVAC study, individuals were vaccinated as part of the National COVID-19 immunization program. To evaluate innate immune responses, blood samples were collected from individuals (20-51 years of age, 15 male, 33 female) before (n=32) and at 1, 2, or 3 days after (n=48) COVID-19 (BNT162b2) vaccination. To monitor the antibody, B and T cell responses blood samples were collected at 28 days after primary and booster vaccination. The innate immune response was characterized by measuring cytokines and chemokines in serum using legendplex, FACS analysis, and RNAseq of peripheral mononuclear cells (PBMCs). Innate immune response early after primary COVID-19 vaccination was characterized by increased serum cytokines/chemokines IFNγ, TNFα, CXCL9, CXCL10, CXCL11 and CCL20. RNA-seq analysis from PBMCs collected before and at 1, 2 or 3 days after vaccination revealed a distinct expression profile associated with inflammatory and interferon gamma response pathways. Cellular analysis showed slightly lower percentage of CD19+ (B cells), CD3+CD4+ (T cells), and CD56+ (NK cells), whereas CD14+ cells (monocytes) were significantly increased in PBMCs shortly after vaccination compared to pre-vaccination samples. Within the monocyte population a significant higher proportion of intermediate monocyte (CD14+CD16+) subset was present. All monocyte subsets showed an activated phenotype with increased expression of co-stimulatory molecules CD80 and/or CD86 after vaccination. The expression of CD80 and CD86 on intermediate monocytes positively associated with SARS-CoV-2 spike-RBD specific antibody levels, measured at day 28 after primary vaccination. Notably, the day of blood sampling proved to be an important confounding factor for the innate responses. The peak of TNFα, IFNγ, CXCL10 and CCL20 was observed on day 1, whereas CXCL11 was most prominent on day 2, and distinct changes in monocyte subpopulations on day 2 post vaccination. Altogether we show that COVID-19 mRNA vaccination induced an a innate immune profile characterized by increased serum cytokines/chemokines, distinct PBMCs transcriptional profile, and changes in the proportion of circulating monocyte subpopulations, some of which correlated with specific antibodies. Although correlation analysis with the T cell responses still need to be completed, we propose using innate immune responses as surrogate of protection which can help in predicting an individual’s (in)ability to mount a proper immune response. 2023 application/pdf 176961 bytes Innate and adaptive immune responses after primary COVID-19 mRNA vaccination in the search for surrogates of vaccine-induced protection