NVX-CoV2373 induces humoral and cellular immune responses that are functionally comparable to vector and mRNA-based vaccines.

Background: After licensing of the protein-based vaccine NVX-CoV2373, three technically different vaccines against the SARS-CoV-2 became available for application to the human population - and for comparison of efficacies. Methods: We here recruited 42 study participants who had obtained one initial dose of NVX-CoV2373 and analyzed their immune responses in contrast to 37 study participants who had obtained either the vector vaccine AZD1222 or the mRNA vaccine BNT162b2 a year earlier. 32 participants also donated blood before first vaccination to serve as a vaccine-naive control. In detail, we investigated and quantified at day 21 and approximately six months after primary immunization the amounts of vaccine-specific antibodies produced, their neutralization capacity, their quality in terms of binding different epitopes and their efficiency in inducing various isotypes. Cellular immunity and intracellular cytokine production following in vitro re-stimulation with BNT162b2 vaccine was analyzed via ELISpot or via flow cytometry. Results: Our results show that even though vaccination including the mRNA vaccine yielded best results in almost any aspect of antibody levels and binding efficiency, the neutralization capacities against the wild-type Wuhan strain and the Omicron BA.1 variant early and at six months were comparable among all three vaccination groups. As for the T cells, we observed a prevailing CD8 response at three weeks which turned into a predominant CD4 memory at six months which has not yet been observed for AZD1222 and BNT162b2. While additional infection with SARS-CoV-2 resulted in a boost for the humoral response, T cell memory appeared rather unaffected. Conclusion: Whether any of these differences translate into real world protection from infection, mitigation of severe disease courses and prevention of long/post COVID will need to be investigated in the future.

The varying extent of humoral and cellular immune responses to either vector- or RNA-based SARS-CoV-2 vaccines persists for at least 18 months and is independent of infection.

The corona virus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2) spurred a worldwide race for the development of an efficient vaccine. Various strategies were pursued; however, the first vaccines to be licensed presented the SARS-CoV-2 spike protein either in the context of a non-replicating adenoviral vector or as an mRNA construct. While short-term efficacies have extensively been characterized, the duration of protection, the need for repeated boosting, and reasonable vaccination intervals have yet to be defined. We here describe the adaptive immune response resulting from homologous and heterologous vaccination regimen at 18 months after primary vaccination. To that extent, we monitored 176 healthcare workers, the majority of whom had recovered from previous SARS-CoV-2 infection. In summary, we find that differences depending on primary immunization continue to exist 18 months after the first vaccination and these findings hold true irrespective of previous infection with the virus. Homologous primary immunization with BNT162b2 was repeatedly shown to produce higher antibody levels and slower antibody decline, leading to more effective in vitro neutralization capacities. Likewise, cellular responses resulting from in vitro re-stimulation were more pronounced after primary immunization involving BNT162b2. In contrast, IL-2 producing memory T helper and cytotoxic T cells appeared independent from the primary vaccination regimen. Despite these differences, comparable infection rates among all vaccination groups suggest comparable real-life protection.IMPORTANCEVaccination against the severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2) was shown to avert severe courses of corona virus disease 2019 (COVID-19) and to mitigate spreading of the virus. However, the duration of protection and need for repeated boosting have yet to be defined. Monitoring and comparing the immune responses resulting from various vaccine strategies are therefore important to fill knowledge gaps and prepare for future pandemics.

A linear B-cell epitope close to the furin cleavage site within the S1 domain of SARS-CoV-2 Spike protein discriminates the humoral immune response of nucleic acid- and protein-based vaccine cohorts.

Background: Understanding the humoral immune response towards viral infection and vaccination is instrumental in developing therapeutic tools to fight and restrict the viral spread of global pandemics. Of particular interest are the specificity and breadth of antibody reactivity in order to pinpoint immune dominant epitopes that remain immutable in viral variants. Methods: We used profiling with peptides derived from the Spike surface glycoprotein of SARS-CoV-2 to compare the antibody reactivity landscapes between patients and different vaccine cohorts. Initial screening was done with peptide microarrays while detailed results and validation data were obtained using peptide ELISA. Results: Overall, antibody patterns turned out to be individually distinct. However, plasma samples of patients conspicuously recognized epitopes covering the fusion peptide region and the connector domain of Spike S2. Both regions are evolutionarily conserved and are targets of antibodies that were shown to inhibit viral infection. Among vaccinees, we discovered an invariant Spike region (amino acids 657-671) N-terminal to the furin cleavage site that elicited a significantly stronger antibody response in AZD1222- and BNT162b2- compared to NVX-CoV2373-vaccinees. Conclusions: Understanding the exact function of antibodies recognizing amino acid region 657-671 of SARS-CoV-2 Spike glycoprotein and why nucleic acid-based vaccines elicit different responses from protein-based ones will be helpful for future vaccine design.

Vaccine-Induced T-Cell and Antibody Responses at 12 Months after Full Vaccination Differ with Respect to Omicron Recognition.

More than a year after the first vaccines against the novel SARS-CoV-2 were approved, many questions still remain about the long-term protection conferred by each vaccine. How long the effect lasts, how effective it is against variants of concern and whether further vaccinations will confer additional benefits remain part of current and future research. For this purpose, we examined 182 health care employees-some of them with previous SARS-CoV-2 infection-12 months after different primary immunizations. To assess antibody responses, we performed an electrochemiluminescence assay (ECLIA) to determine anti-spike IgGs, followed by a surrogate virus neutralization assay against Wuhan-Hu-1 and B.1.1.529/BA.1 (Omicron). T cell response against wild-type and the Omicron variants of concern were assessed via interferon-gamma ELISpot assays and T-cell surface and intracellular cytokine staining. In summary, our results show that after the third vaccination with an mRNA vaccine, differences in antibody quantity and functionality observed after different primary immunizations were equalized. As for the T cell response, we were able to demonstrate a memory function for CD4+ and CD8+ T cells alike. Importantly, both T and antibody responses against wild-type and omicron differed significantly; however, antibody and T cell responses did not correlate with each other and, thus, may contribute differentially to immunity.

Higher SARS-CoV-2 Spike Binding Antibody Levels and Neutralization Capacity 6 Months after Heterologous Vaccination with AZD1222 and BNT162b2.

Within a year after the emergence of SARS-CoV-2, several vaccines had been developed, clinically evaluated, proven to be efficacious in preventing symptomatic disease, and licensed for global use. The remaining questions about the vaccines concern the duration of protection offered by vaccination and its efficacy against variants of concern. Therefore, we set out to analyze the humoral and cellular immune responses 6 months into homologous and heterologous prime-boost vaccinations. We recruited 190 health care workers and measured their anti-spike IgG levels, their neutralizing capacities against the Wuhan-Hu-1 strain and the Delta variant using a surrogate viral neutralization test, and their IFNγ-responses towards SARS-CoV-2-derived spike peptides. We here show that IFNγ secretion in response to peptide stimulation was significantly enhanced in all three vaccination groups and comparable in magnitude. In contrast, the heterologous prime-boost regimen using AZD1222 and BNT162b2 yielded the highest anti-spike IgG levels, which were 3-4.5 times more than the levels resulting from homologous AZD1222 and BNT162b2 vaccination, respectively. Likewise, the neutralizing capacity against both the wild type as well as the Delta receptor binding domains was significantly higher following the heterologous prime-boost regimen. In conclusion, our results suggest that mixing different SARS-CoV-2 vaccines might lead to more efficacious and longer-lasting humoral protection against breakthrough infections.