Longitudinal monitoring of mRNA-vaccine-induced immunity against SARS-CoV-2.

Background: Worldwide vaccination campaigns significantly reduced mortality caused by SARS-CoV-2 infection and diminished the devastating effects of the pandemic. The first approved vaccines are based on novel mRNA technology and elicit potent immune responses offering high levels of protection from severe disease. Methods: Here we longitudinally assessed adaptive immune responses during a 12-month follow-up period after the initial immunization with 2 doses of mRNA vaccines and after the booster dose in blood and saliva. Results: Our findings demonstrate a rapid waning of the anti-spike IgG titers between months 3 and 6 after the initial vaccination (1.7- and 2.5-fold decrease in plasma and saliva, respectively; P<0.0001). Conversely, the frequency of spike-specific memory B cells increased during this period (2.4-fold increase; P<0.0001) while the frequency of spike-specific CD4+ and CD8+ T cells remained stable for all assessed functions: cytotoxicity, IFNγ, IL-2, and TNFα expression. Booster vaccination significantly improved the antibody response in plasma and saliva, with the most profound changes observed in the neutralization capacity against the currently circulating omicron variant (25.6-fold increase; P<0.0001). The positive effect of booster vaccination was also evident for spike-specific IgG+ memory B cell (2.4-fold increase; P<0.0001) and cytotoxic CD4+ and CD8+ T cell responses (1.7- and 1.9-fold increase respectively; P<0.05). Conclusions: Collectively, our findings offer a detailed insight into the kinetics of adaptive immune response following SARS-CoV-2 vaccination and underline the beneficial effects of a booster vaccination.

Longitudinal monitoring of mRNA-vaccine-induced immunity against SARS-CoV-2

Background Worldwide vaccination campaigns significantly reduced mortality caused by SARS-CoV-2 infection and diminished the devastating effects of the pandemic. The first approved vaccines are based on novel mRNA technology and elicit potent immune responses offering high levels of protection from severe disease. Methods Here we longitudinally assessed adaptive immune responses during a 12-month follow-up period after the initial immunization with 2 doses of mRNA vaccines and after the booster dose in blood and saliva. Results Our findings demonstrate a rapid waning of the anti-spike IgG titers between months 3 and 6 after the initial vaccination (1.7- and 2.5-fold decrease in plasma and saliva, respectively;P<0.0001). Conversely, the frequency of spike-specific memory B cells increased during this period (2.4-fold increase;P<0.0001) while the frequency of spike-specific CD4+ and CD8+ T cells remained stable for all assessed functions: cytotoxicity, IFNγ, IL-2, and TNFα expression. Booster vaccination significantly improved the antibody response in plasma and saliva, with the most profound changes observed in the neutralization capacity against the currently circulating omicron variant (25.6-fold increase;P<0.0001). The positive effect of booster vaccination was also evident for spike-specific IgG+ memory B cell (2.4-fold increase;P<0.0001) and cytotoxic CD4+ and CD8+ T cell responses (1.7- and 1.9-fold increase respectively;P<0.05). Conclusions Collectively, our findings offer a detailed insight into the kinetics of adaptive immune response following SARS-CoV-2 vaccination and underline the beneficial effects of a booster vaccination.

SARS-CoV-2 humoral and cellular immunity following different combinations of vaccination and breakthrough infection.

The elicited anti-SARS-CoV-2 immunity is becoming increasingly complex with individuals receiving a different number of vaccine doses paired with or without recovery from breakthrough infections with different variants. Here we analyze the immunity of individuals that initially received two doses of mRNA vaccine and either received a booster vaccination, recovered from a breakthrough infection, or both. Our data suggest that two vaccine doses and delta breakthrough infection or three vaccine doses and optionally omicron or delta infection provide better B cell immunity than the initial two doses of mRNA vaccine with or without alpha breakthrough infection. A particularly potent B cell response against the currently circulating omicron variant (B. 1.1.529) was observed for thrice vaccinated individuals with omicron breakthrough infection; a 46-fold increase in plasma neutralization compared to two vaccine doses (p < 0.0001). The T cell response after two vaccine doses is not significantly influenced by additional antigen exposures. Of note, individuals with hybrid immunity show better correlated adaptive immune responses compared to those only vaccinated. Taken together, our data provide a detailed insight into SARS-CoV-2 immunity following different antigen exposure scenarios.

Detectable SARS-CoV-2 RNAemia in Critically Ill Patients, but Not in Mild and Asymptomatic Infections.

BACKGROUND: The SARS-CoV-2 pandemic has challenged many of our current routine practices in the treatment and care of patients. Given the critical importance of blood donation and transfusion we analyzed 92 blood samples of individuals infected with SARS-CoV-2 stratified by symptoms. STUDY DESIGN AND METHODS: We therefore tested blood samples for SARS-CoV-2 via RT-PCR targeting the E gene. In addition, we tested each blood sample for anti-SARS-CoV-2 IgG antibodies via ELISA and performed plaque reduction neutralization tests. RESULTS: SARS-CoV-2 RNA was absent in the blood of mild to asymptomatic patients (57 individuals) and only detectable in individuals with severe COVID-19 who were admitted to the intensive care unit (35 individuals) (n = 6/92 [6.5%]; p = 0.023 Fisher's exact test). Interestingly, anti-spike IgG antibodies were not significantly higher in intensive care unit patients compared to mild patients, but we found that their neutralizing capacity was disproportionately increased (p < 0.001). CONCLUSION: Our observations support the hypothesis that there are no potential hazards from blood or plasma transfusion of SARS-CoV-2-positive individuals with mild flu-like symptoms and more importantly of asymptomatic individuals.