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1.
Medical Immunology (Russia) ; 24(3):629-640, 2022.
Article in Russian | EMBASE | ID: covidwho-2006567

ABSTRACT

The relevance of the current epidemic situation of a new coronavirus infection is determined by new strains of the virus and the registration of cases of re-infection in COVID-19 survivors earlier. In this regard, the questions about the expediency and nature of vaccination of those who have been ill attract close attention, moreover it has affected the formation of the concept of “hybrid immunity”. The aim of this study was to analyze changes in the parameters of the immune system, reflecting their regulatory and functional potential, in response to the introduction of the peptide vaccine EpiVacCorona to persons who have suffered from the new coronavirus infection. To study the features of the formation of hybrid immunity, a retrospective analysis of the observation of 43 study participants was carried out. The inclusion criteria were data confirming COVID-19 in mild and moderate forms of the course in the period from six months to a year ago, a low level or absence of antibodies to the nucleocapsid protein SARS-CoV-2, a negative PCR result for the presence of the SARS-CoV-2 virus, the absence of comorbid pathology. The subpopulation composition, regulatory and functional potential of the immune system were determined by flow cytofluorimetry using a set of monoclonal antibodies corresponding to the goals. 21 days after the administration of a single dose of EpiVacCorona, antibodies to the vaccine peptide antigens were registered in all study participants at the highest coefficient of positivity values for the SARS-CoV-2-IgG-Vector test system used. In addition, there was a fourfold increase in the number of specific IgG to the N protein. A specific immune response to recombinant SARS-CoV-2 antigens was accompanied by a decrease in the circulation of the number of monocytes expressing TLR4, T helper cells expressing the interaction coreceptor with antigen-presenting cells, unconnected B memory with an increase in the number of B lymphocytes expressing the CD40 T-B coreceptor interaction molecule. The remaining differences in the functioning of the immune system identified in patients with COVID-19 before the vaccination in comparison with the control data have not changed. The differences consist in a decrease in the proportion of monocytes expressing HLA-DR, an increase in the expression of interaction molecules on T and B lymphocytes, an increase in the number of Treg, B1 cells, activated B lymphocytes with a decrease in the proportion of suppressor Breg and B memory. The totality of the presented data demonstrates that the COVID-19 infection that preceded vaccination in mild and moderate clinical course contributes to the formation of immunological memory, which made it possible to form a secondary immune response even to a single injection of peptide antigens of the virus.

2.
Medical Immunology (Russia) ; 24(2):367-378, 2022.
Article in Russian | EMBASE | ID: covidwho-1897222

ABSTRACT

The dominance of reliably immunized population is a fundamental factor in prevention of COVID-19 pandemia, with immune prophylaxis taking a dominant position. Due to lack of clear data on the intensity of specific immunity after a new coronavirus infection, consolidation of immunological memory by vaccination becomes the urgent task, in order to exclude the risk of re-involvement of previously ill patients into the epidemic process. Meanwhile, many questions related to vaccination of COVID-19 survivors do not get distinct answers. To study the features of immune response, using a vaccine based on SARS-CoV-2 peptide antigens (EpiVacCorona), we monitored 81 participants. The inclusion criteria were data confirming COVID-19 in the anamnesis (medical documentation), low levels or absence of antibodies to the SARS-CoV-2 nucleocapsid protein, and negative PCR tests for SARS-CoV-2. When assessing the data of post-vaccinal immunity checked 21 days after 1st dose of the vaccine, the patients were divided into 2 groups: those who did not respond, and those who developed the immune response. In order to identify possible reasons for different phenotypic patterns of humoral response to vaccination, a comparative analysis of B lymphocyte indexes was carried out in these groups. Absolute counts, subpopulation composition and activation potential of peripheral blood B lymphocytes were determined by flow cytofluorometry using appropriate labeled monoclonal antibodies purchased from Beсkman Coulter. Comparative analysis of B lymphocyte indexes on the day of first vaccination showed that the persons who did not respond to the vaccine had smaller counts of circulating B cells, i.e., both percentage and absolute cell numbers, than in comparison group, as well as changed ratio of B1-to-B2 subpopulations. After administration of the first vaccine dose (by day +21), in alternative variant of the antibody response to V1, the differences in the parameters of B cells were presented as a smaller percentage and absolute numbers of regulatory B lymphocytes in non-responding participants. Moreover, the contents of minor B cell subpopulations were decreased in the non-responding group than in the comparison group, thus affecting the values of the B1:B2 ratio. In general, the presented data demonstrate that the absence of secondary immune response to antigens of the SARS-CoV-2 peptide vaccine could be is associated with altered differentiation of B1 and B2 subpopulations, B regulatory lymphocytes, B memory cells.

3.
Topics in Antiviral Medicine ; 30(1 SUPPL):121, 2022.
Article in English | EMBASE | ID: covidwho-1880045

ABSTRACT

Background: SARS-CoV-2 produces variable immune responses leading to different levels of immune protection. The relationship between neutralizing antibody level (NAb) and protective immunity has been well characterized after infection and vaccination. While comparatively specific T cell responses tend to be more variable, the impacts of these responses have broad implications on long-term immunity and their role in protective immunity has not been as clearly defined. Using data from our prospective cohort study and studies of clinical protective immunity/efficacy (from vaccines), we predicted protective immunity over time in relation to SARS-CoV-2-specific T cell dynamics. Methods: With linear mixed-effects models from our published immune data from people recovering from COVID-19, we simulated the Spike (S)-specific interferon-γ (IFNγ)+ CD4+, S-specific IFNγ+ CD8+, and nucleocapsid (N)-specific IFNγ+ CD8+ T cells over time (n=500 individuals). We then predicted NAbs from linear regression models developed from the same cohort. Finally, protective immunity from NAb titers was simulated from a published model. We similarly simulated 25, 50, and 75% lower T cell responses than those observed post-COVID-19 to understand how immune response variation may impact protective immunity. Results: Virus-specific T cell responses resulted in similar protective immunity across T cell subsets, but with differences in variability over time. Protective immunity for IFNγ+ S CD8 T cells spanned from 86-95%, while for IFNγ+ S CD4 T cells and IFNγ+ N CD4 T cells it ranged from 81-96% and 84-95% respectively. Further, based on simulated dampened T cell responses, protective immunity overall did not drop below 81% less than nine months after infection even with a 75% reduction in specific T cell immunity. Conclusion: NAbs are often the singular focus to predict protective immunity and the role of virus-specific T cell immunity has often been discussed as a secondary immune response. Our analysis demonstrates that for SARS-CoV-2, certain T cells responses can reliably predict protective immunity and may be intrinsically linked. Simulating dampened T cell response to mimic a more virulent strain or inadequate immune response, demonstrated that dampened T cell response may not be responsible for inadequate protective immunity in these scenarios. In the absence of prospective clinical data, similar models may be utilized to explore the impact of potential therapeutics on immune responses and resulting protective immunity.

4.
International Journal of Infectious Diseases ; 116:S63, 2022.
Article in English | EMBASE | ID: covidwho-1734443

ABSTRACT

Purpose: The dosing interval for AZD1222/Covishield vaccine was prolonged for ≥16 weeks, due to short supply in Sri Lanka. As robust secondary immune response depends on the presence of memory B cell (Bmem), we investigated their frequency following a single dose of the AZD1222. Methods & Materials: Bmem responses were assessed to S1, S2 and N protein of the SARS-CoV-2 by B cell ELISpot assays in 45 individuals after ≥16 weeks of receiving a single dose of the vaccine. The mean±2 SD of the background responses was defined as the threshold for positive response of antibody secreting cells (ASCs)/1 million cells. Results: In this cohort, 40/45 (88.9%) individuals responded to S1, 39/45 (86.7%) to S2 and 36/45 (80%) to N. Responses to S1 (p<0.0001, median 90, IQR 50 to 137.5 ASCs/1 million cells) and S2 (p=0.0067, median 70, IQR 47.5 to 97.5 ASCs/1 million cells) were significantly higher than N (median 50, IQR 22.5 to 80 ASCs/1 million cells). A significant difference in the frequency of responses to S1 (p=0.0017) and S2 (p=0.046), were seen in different age groups, with a higher frequency of ASCs to S1 and S2 proteins in individuals age between 40-60 and >60 years of age, compared to younger individuals. There was a significant, positive correlation for the frequency of ASCs to S1 (Spearman's r=0.49, p=0.0007), S2 (Spearman's r=0.32, p=0.0308) and N (Spearman's r=0.33, p=0.0274) with age. Conclusion: 86.7% to 88.9% of individuals had Bmem to the spike protein of the virus, suggesting that a single dose of the vaccine, induced potent Bmem responses. Although 80% of individuals had a low frequency of responses to the N protein, which was not present in the vaccine, this could be due to the presence of cross reactive Bmem responses to N protein of previous beta-coronavirus infections, in older individuals.

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