An efficient immunoassay for the B cell help function of SARS-CoV-2-specific memory CD4+ T cells.

The B cell "help" function of CD4+ T cells is an important mechanism of adaptive immunity. Here, we describe improved antigen-specific T-B cocultures for quantitative measurement of T cell-dependent B cell responses, with as few as ∼90 T cells. Utilizing M. tuberculosis (Mtb), we show that early priming and activation of CD4+ T cells is important for productive interaction between T and B cells and that similar effects are achieved by supplementing cocultures with monocytes. We find that monocytes promote survivability of B cells via BAFF and stem cell growth factor (SCGF)/C-type lectin domain family 11 member A (CLEC11A), but this alone does not fully recapitulate the effects of monocyte supplementation. Importantly, we demonstrate improved activation and immunological output of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific memory CD4+ T-B cell cocultures with the inclusion of monocytes. This method may therefore provide a more sensitive assay to evaluate the B cell help quality of memory CD4+ T cells, for example, after vaccination or natural infection.

Inactivated whole-virion vaccine BBV152/Covaxin elicits robust cellular immune memory to SARS-CoV-2 and variants of concern.

BBV152 is a whole-virion inactivated vaccine based on the Asp614Gly variant. BBV152 is the first alum-imidazoquinolin-adjuvanted vaccine authorized for use in large populations. Here we characterized the magnitude, quality and persistence of cellular and humoral memory responses up to 6 months post vaccination. We report that the magnitude of vaccine-induced spike and nucleoprotein antibodies was comparable with that produced after infection. Receptor binding domain-specific antibodies declined against variants in the order of Alpha (B.1.1.7; 3-fold), Delta (B.1.617.2; 7-fold) and Beta (B.1.351; 10-fold). However, pseudovirus neutralizing antibodies declined up to 2-fold against the Delta followed by the Beta variant (1.7-fold). Vaccine-induced memory B cells were also affected by the Delta and Beta variants. The SARS-CoV-2-specific multicytokine-expressing CD4+ T cells were found in ~85% of vaccinated individuals. Only a ~1.3-fold reduction in efficacy was observed in CD4+ T cells against the Beta variant. We found that antigen-specific CD4+ T cells were present in the central memory compartment and persisted for at least up to 6 months post vaccination. Vaccine-induced CD8+ T cells were detected in ~50% of individuals. Importantly, the vaccine was capable of inducing follicular T helper cells that exhibited B-cell help potential. These findings show that inactivated vaccine BBV152 induces robust immune memory to SARS-CoV-2 and variants of concern that persists for at least 6 months after vaccination.

An efficient immunoassay for the B-cell help function of SARS-CoV-2 specific memory CD4+ T cells

The B cell “help” function of CD4+ T cells is an important mechanism of adaptive immunity. Here, we describe improved antigen-specific T-B co-cultures for quantitative measurement of T cell-dependent B cell responses, with as few as ∼90 T cells. Utilizing Mtb, we show that early priming and activation of CD4+ T cells is important for productive interaction between T and B cells, and that similar effects are achieved by supplementing co-cultures with monocytes. We find that monocytes promote survivability of B cells via BAFF and SCGF/CLEC11A, but this alone does not fully recapitulate the effects of monocyte-supplementation. Importantly, we demonstrate improved activation and immunological output of SARS-CoV-2 specific memory CD4+ T - B cell co-cultures with the inclusion of monocytes. This method may therefore provide a more sensitive assay to evaluate the B cell help quality of memory CD4+ T cells, for example after vaccination or natural infection. Graphical Ansari et al. describe an efficient T-B cell co-culture assay to assess B-cell help function of antigen-specific T helper cells in healthy and COVID-19 recovered individuals, based on the inclusion of monocytes. Increased B cell output in this assay may provide extra sensitivity to evaluate immunological responses in different contexts.

Immune Memory in Mild COVID-19 Patients and Unexposed Donors Reveals Persistent T Cell Responses After SARS-CoV-2 Infection.

Understanding the causes of the diverse outcome of COVID-19 pandemic in different geographical locations is important for the worldwide vaccine implementation and pandemic control responses. We analyzed 42 unexposed healthy donors and 28 mild COVID-19 subjects up to 5 months from the recovery for SARS-CoV-2 specific immunological memory. Using HLA class II predicted peptide megapools, we identified SARS-CoV-2 cross-reactive CD4+ T cells in around 66% of the unexposed individuals. Moreover, we found detectable immune memory in mild COVID-19 patients several months after recovery in the crucial arms of protective adaptive immunity; CD4+ T cells and B cells, with a minimal contribution from CD8+ T cells. Interestingly, the persistent immune memory in COVID-19 patients is predominantly targeted towards the Spike glycoprotein of the SARS-CoV-2. This study provides the evidence of both high magnitude pre-existing and persistent immune memory in Indian population. By providing the knowledge on cellular immune responses to SARS-CoV-2, our work has implication for the development and implementation of vaccines against COVID-19.