Anti-SARS-CoV-2 vaccination leads to the production of neutralizing as well as non-neutralizing antibodies. In the current study, we investigated the temporal dynamics of both sides of immunity after vaccination with two doses of Sputnik V against SARS-CoV-2 variants Wuhan-Hu-1 SARS-CoV-2 G614-variant (D614G), B.1.617.2 (Delta), and BA.1 (Omicron). First, we constructed a SARS-CoV-2 pseudovirus assay to assess the neutralization activity of vaccine sera. We show that serum neutralization activity against BA.1 compared to D614G is decreased by 8.16-, 11.05-, and 11.16- fold in 1, 4, and 6 months after vaccination, respectively. Moreover, previous vaccination did not increase serum neutralization activity against BA.1 in recovered patients. Next, we used the ADMP assay to evaluate the Fc-mediated function of vaccine-induced serum antibodies. Our results show that the antibody-dependent phagocytosis triggered by S-proteins of the D614G, B.1.617.2 and BA.1 variants did not differ significantly in vaccinated individuals. Moreover, the ADMP efficacy was retained over up to 6 months in vaccine sera. Our results demonstrate differences in the temporal dynamics of neutralizing and non-neutralizing antibody functions after vaccination with Sputnik V.

Background/Objectives: CTLA4 (Cytotoxic T-Lymphocyte Antigen 4) is a key immune checkpoint that plays a principal part in controlling T-cell activation and maintaining immune homeostasis. CTLA4 haploinsufficiency (CTLA4^+/−) results in severe autoimmune disorders and increased susceptibility to infections, often associated with dysregulated T cell activity. CTLA4^+/− patients experience life-threatening complications and exhibit moderate survival rates that can vary significantly, depending on the treatment of associated autoimmune phenotypes. Current therapeutic approaches primarily use immunosuppressives and monoclonal antibodies to modulate the immune response; however, their effectiveness and specificity are often limited. In this study, we aimed to develop a novel therapy approach for CTLA4 haploinsufficiency utilizing the CRISPR activation system (CRISPRa) to enhance wild-type CTLA4 allele expression. Methods: The CRISPR/Cas9 system has become a widely used method for precise genome editing, allowing for targeted gene regulation. We applied a CRISPRa-based strategy to induce endogenous CTLA4 expression using appropriate cellular models and evaluated transcriptomic changes. Results: CRISPRa-mediated activation enabled increased CTLA4 expression, suggesting the feasibility of restoring physiological expression levels. Conclusions: This approach may provide a basis for developing CRISPRa-based strategies to restore immune regulation and improve clinical outcomes in CTLA4^+/− patients.