ABSTRACT
AO_SCPLOWBSTRACTC_SCPLOWVaccination elicits a complex combination of immune responses. Immune memory formation is observed not only in the antibody responses of B-cells, but also in the T-cell response. Moreover, some live attenuated vaccines such as measles-containing vaccines can induces heterologous protection, likely through induction of memory characteristics in the innate immune response. Little is known about the immunological interaction that may occur when different vaccines are administered soon after one another, especially in relation to the novel COVID-19 vaccines. The aim of this study was to compare the innate and adaptive immune responses between persons randomized to receive either a MMR or a placebo (0.9% NaCl) injection prior to their SARS-CoV-2 mRNA vaccination. We compared: i) the cytokine and chemokine production (tumor necrosis factor [TNF]-, interleukin [IL]-1{beta}, IL-6, IL-10, IL-17, IL-22, interferon [IFN]- and IFN-{gamma}) after in-vitro stimulation of peripheral blood mononuclear cells (PBMCs) with heterologous stimuli (severe acute respiratory syndrome coronavirus [SARS-CoV]-2, measles mumps and rubella [MMR] vaccine, Toll-like receptor [TLR]-3 ligand, TLR-7/8 ligand, or TLR-4 ligand), and ii) the SARS-CoV-2 neutralizing antibody responses. Ninety-five participants in the CROWN CORONATION trial (NCT04333732; a randomized control trial comparing MMR to placebo for prevention of COVID-19) agreed to an additional single blood sample collection for this immunological study. Samples were collected around 196 (SD 22) days after administration of MMR or placebo, and around 105 (SD 27) days after their second SARS-CoV-2 mRNA vaccine injection. Twenty-four percent of participants were older than fifty and sixty-seven percent were female. The median TNF- response to stimulation with MMR was 8315.3 pg/mL in the MMR group and 4340.5 pg/mL in the placebo group; adjusted median difference (95% CI) 3012.5 (-4734.1; -323.5); p=0.017. No other significant differences were noted in the cytokine and chemokine responses between treatment groups. The SARS-CoV-2 neutralization assay geometric mean (SD) IC50 in the MMR group was 507.6 (2.6) and in the placebo group was 515.7 (2.2); ratio of geometric means (95% CI) 1.0 (0.7; 1.5). Pre-exposure to MMR vaccine was generally not associated with changes in cytokine and chemokine responses of stimulated PBMCs at 105 (27) days after SARS-CoV-2 mRNA vaccination. MMR vaccination led only to an increase of TNF- production in response to an additional ex-vivo stimulation with the MMR vaccine. The SARS-CoV-2 neutralization IC50 values did not differ between MMR and placebo groups. Further studies using a repeated measures design would be better suited to explore or rule-out any short-lived vaccine response and vaccine-vaccine immunological interaction.
