ABSTRACT
Determining SARS-CoV-2 immunity is critical to assess COVID-19 risk and the need for prevention and mitigation strategies. We measured SARS-CoV-2 Spike/Nucleocapsid seroprevalence and serum neutralizing activity against Wu01, BA.4/5 and BQ.1.1 in 1,411 individuals who received medical treatment in five emergency departments in North Rhine-Westphalia, Germany. We detected Spike-IgG in 95.6%, Nucleocapsid-IgG in 24.0% and neutralization against Wu01, BA.4/5 and BQ.1.1 in 94.4%, 85.0%, and 73.8% of participants, respectively. Neutralization against BA.4/5 and BQ.1.1 was reduced 5.6- and 23.4-fold compared to Wu01. Accuracy of S-IgG detection for determination of neutralizing activity against BQ.1.1 was reduced substantially. Furthermore, we explored previous vaccinations and infections as most important correlates of improved BQ.1.1 neutralization using multivariable and Bayesian network analyses. Given an adherence to COVID-19 vaccination recommendations of only 67.7% of all participants, we highlight the need for improvement of vaccine-uptake to reduce the COVID-19 risk in upcoming infection-waves with immune evasive variants.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
The elicited anti-SARS-CoV-2 immunity worldwide is becoming increasingly complex with individuals receiving a different amount of vaccine doses paired with or without recovery from breakthrough infections with different variants. To understand the variety of anti-SARS-CoV-2 immunity we analyzed the adaptive immune responses of individuals that initially received 2 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 2 doses of mRNA vaccine with or without alpha breakthrough infection. A particularly potent humoral response against the currently circulating omicron variant was observed for the thrice vaccinated individuals with omicron breakthrough infection; a 46-fold increase in neutralization compared to 2 vaccine doses (P < 0.0001). The same group also had the highest titer of spike-specific antibodies in saliva and highest frequency of spike-specific memory B cells in peripheral blood; 9.5-fold (P < 0.001) and 3.5-fold (P < 0.05) increase compared to 2 vaccine doses. The T cell response after two vaccine doses was not significantly influenced by additional immunizations. Of note, individuals with hybrid immunity showed better coordination of the adaptive immune response compared to those only vaccinated. Taken together, our data provide a detailed insight into the SARS-CoV-2 immunity following different immunization scenarios.