ABSTRACT
BackgroundCurrently used vaccines to protect from COVID-19 mostly focus on the receptor-binding domain (RBD) of the viral spike protein, and induced neutralizing antibodies have shown to be protective. However, functional relevance of vaccine-generated antibodies are poorly understood on variants-of-concern (VOCs) and mucosal immunity. MethodsWe compared specific antibody production against the S1 subunit and the RBD of the spike protein, the whole virion of SARS-CoV-2, and monitored neutralizing antibodies in sera and saliva of 104 BNT162b2 vaccinees and 57 individuals with natural SARS-CoV-2 infection. Furthermore, we included a small cohort of 11 individuals which received a heterologous ChAdOx1-S/BNT162b2 prime-boost vaccination. ResultsVaccinated individuals showed higher S1-IgG antibodies in comparison to COVID-19 patients, followed by a significant decrease 3 months later. Neutralizing antibodies (nAbs) were poorly correlated with initial S1-IgG levels, indicating that these might largely be non-neutralizing. In contrast, RBD IgGAM was strongly correlated to nAbs, suggesting that RBD-IgGAM is a surrogate marker to estimate nAb concentrations after vaccination. The protective effect of vaccine- and infection-induced nAbs was found reduced towards B.1.617.2 and B.1.351 VOCs. NAb titers are significantly higher after third vaccination compared to second vaccination. In contrast to COVID-19 patients, no relevant levels of RBD specific antibodies were detected in saliva samples from vaccinees. ConclusionsOur data demonstrate that BNT162b2 vaccinated individuals generate relevant neutralizing antibodies, which begin to decrease within three months after immunization and show lower neutralizing potential to VOCs as compared to the original Wuhan virus strain. A third booster vaccination provides a stronger nAb antibody response than the second vaccination. The systemic vaccine does not seem to elicit readily detectable mucosal immunity.
ABSTRACT
Advantages of DNA vaccination against infectious diseases over more classical immunization methods include the possibilities for rapid manufacture, fast adaptation to newly emerging pathogens and high stability at ambient temperatures. In addition, upon DNA immunization the antigen is produced by the cells of the vaccinated individual, which leads to activation of both cellular and humoral immune responses due to antigen presentation via MHC I and MHC II molecules. However, so far DNA vaccines have shown most efficient immunogenicity mainly in small rodent models, whereas in larger animals including humans there is still the need to improve effectiveness. This is mostly due to inefficient delivery of the DNA plasmid into cells and nuclei. Here, we discuss technologies used to overcome this problem, including physical means such as in vivo electroporation and co-administration of adjuvants. Several of these methods have already entered clinical testing in humans.
