Further work is required to comprehensively characterise the epitope repertoire elicited by SARS-CoV-2 infection in the context of a broad set of HLA alleles to define patterns of immunodominance
Further work is required to comprehensively characterise the epitope repertoire elicited by SARS-CoV-2 infection in the context of a broad set of HLA alleles to define patterns of immunodominance. Our data indicate that antibody and T cell reactions in convalescent individuals with predominately slight disease can be uncoupled. demonstrated for SARS-CoV-2 ORF3a, ORF6, ORF7, ORF8 and Env between HIV bad (green) and HIV positive (reddish). (n=30 per group). (C) Magnitude of the total SARS-CoV-2 reactions analyzed in pre-pandemic samples, confirmed SARS-CoV-2 and suspected instances with clinical definition but found to be SARS-CoV-2 seronegative on testing. In suspected instances, orange dots depict HIV bad and brownish dots HIV positive donors. Correlation between CD4:CD8 percentage in HIV infected individuals with their (D) Nucleocapsid and (E) Membrane reactions, depicting disease severity per donor. Correlation of total SARS-CoV-2 reactions with age in (F) HIV bad and (G) HIV positive, depicting disease severity per donor. (H) Rabbit Polyclonal to CLTR2 Correlation of total SARS-CoV-2 reactions with DPSO in HIV bad and (J) HIV positive, depicting disease severity per donor. (J) Magnitude of the total SARS-CoV-2 reactions by ethnicity and (K) gender between HIV bad and HIV positive. The non-parametric Spearman test was utilized for correlation analysis. Two-way ANOVA was utilized for group assessment. *p < 0.05, **p<0.01. Fig. S3. Cytokine profile of SARS-CoV-2-, CMV- and Gag- specific T CFTRinh-172 cells (A) Rate of recurrence of SARS-CoV-2-specific CD154+ CD4 T cells recognized by manifestation of IFN-+, IL-2+, or TNF-+ or overall reactions with at least one of the three cytokines (IFN-, TNF- and IL-2) against Spike (S1 and S2 swimming pools) (B) M/N or (C) combined (Spike and M/N) reactions in HIV-negative (HIV-, n=12) and HIV positive individuals (HIV+, n=11) recovering from COVID-19 disease. (D) Representative circulation plots and summary data (E) showing frequencies of overall (CD154+IFN-+, CD154+IL-2+, or CD154+TNF-+) SARS-CoV-2-, CMV-, or Gag-specific CD4 T cell reactions in the study organizations. (F) Rate of recurrence of SARS-CoV-2-specific CD8 T cells recognized by manifestation of IFN-+, IL-2+ or TNF-+, or overall reactions with at least one of the three cytokines (IFN-, TNF- and IL-2) against Spike (S1 and S2 swimming pools) (G) M/N (H) or combined (Spike and M/N) reactions in HIV-negative (HIV-, n=12) and HIV-seropositive individuals (HIV+, n=11). (I) Representative circulation plots and (J) summary data showing frequencies of overall (IFN-+, IL-2+, or TNF-+) SARS-CoV-2-, CMV-, or Gag-specific CD8 T cell reactions in the study organizations. Error bars symbolize SEM. The non-parametric Spearman test was utilized for correlation analysis; p ideals for individual correlation analysis within organizations, HIV? (green) or HIV+ (reddish) or combined correlation analysis (black) are offered. Significance determined by Mann-Whitney test or Wilcoxon matched- pairs authorized rank test, *p<0.05, **p<0.01, ***p < 0.001. Fig. S4. Association between T cell immunophenotyping and SARS-CoV-2 adaptive immune reactions (A) Representative circulation plots and (B) summary data of the rate of recurrence of CD38+ HLADR+ CD4 and CD8 T cells, and correlations between percentage of CD38+ HLADR+ CD4 and CD8 CFTRinh-172 T cells and total SARS-CoV-2-specific T cell reactions in HIV-seronegative (HIV?, n=26) and HIV positive individuals (HIV+, n=19). (C) Representative circulation plots and (D) summary data of rate of recurrence of PD-1+ TIGIT+ CD4 and CD8 T cells, and correlations between percentage of PD-1+ TIGIT+ CD4 and CD8 T cells and total SARS-CoV-2-specific T cell reactions. (E) Representative circulation plots showing the gating strategy used CFTRinh-172 to define total circulating and triggered Tfh subsets in the study groups and summary data. (F) Correlations between percentage of triggered Tfh and S1 IgG or N IgG titers. Significance determined by Mann-Whitney test, *p<0.05, **p<0.01, ***p < 0.001. The non-parametric Spearman test was utilized for correlation analysis; combined correlation analysis is definitely depicted. NIHPP2021.02.15.431215-product-1.pdf (3.4M) GUID:?E7508DB8-03DC-4DD1-89BC-1E50AA96597C Abstract There is an urgent need to understand the nature of immune responses generated against SARS-CoV-2, to better inform risk-mitigation strategies for people living with HIV (PLWH). Although not all PLWH are considered immunosuppressed, residual cellular immune deficiency and ongoing swelling could.