3. Results
The Activation Induced Marker (AIM) assay revealed circulating memory Tfh (cTfh) cells responded better to the spike proteins of wild type SARS-CoV2 virus compared to the delta strain in naïve vaccinees(Fig 1B-C, G) . There was no difference in cTfh response between the spike proteins of the wild and delta strain in convalescent vaccinees (Fig 1D-E, H) . The breadth of AIM response of cTfh cells to delta spike protein was higher in convalescent vaccinees compared to naïve vaccinees (Fig 1J) . The magnitude of response to wild type spike protein did not show difference between the two groups but both the groups responded to the wild type spike protein(Fig 1I) . We also observed an increase in central memory compartment (CCR7+CD45RA-) in CD4+ T cells in response to the Spike wild type protein in infection naïve vaccinees (Fig K-L, O) while convalescent vaccinees did not show any difference (Fig M-N, P ). When we investigated the antigen specific cytokine response from cTfh, both naive vaccinees and convalescent vaccinees showed higher expression of IL-21 when stimulated with wild type spike protein than to delta spike protein (Fig 2B-E, G-H) . But expression of IL-21 was significantly higher in naïve vaccinees compared to convalescent vaccinees both for wild type and delta type, thought it was not statistically significant for delta spike (Fig 2 I-J) . The neuralization activity did not show any difference between naïve vaccinees or convalescent vaccinees (Fig 2K) but it positively correlated with IL-21 expression from cTfh cells from naïve vaccinees(Fig 2L-M) . Furthermore, our phenotyping of spike specific cTfh from both the groups were biased towards cTfh2 phenotype which is CXCR3-/CCR6- cells (Fig 2N-O).
Our multiplex data revealed that low level of inflammation was still ongoing in these convalescent vaccinees as they displayed higher levels of IL-6 and IL-1β compared to naïve vaccinees (Fig 3H-I) . On the other hand, Tfh promoting cytokines like IL-21, IL-4 and IL-10(Fig 3A-C) and anti-viral memory response inducing cytokines like IFN-γ, IL-15, IL-12(Fig 3D-F) were elevated in naïve vaccinees as compared to convalescent vaccines. All the above data indicated that though cTfh cells from convalescent vaccinees recognizes both wild type and delta spike proteins, their response is low compared to naïve vaccinees.