Thread by @kedzierskalab

Children infected with #SARSCoV2 mount a rapid immune response that may limit the development of immune “memory”, supporting #COVID19 #vaccines for children -a 🧵⬇️ on our @ImmunityCP paper go.unimelb.edu.au/v4je @louiserowntree @KatherineKedz @CvandeSandt @TheDohertyInst (1/14)

We directly assessed ex vivo CD8+ T cell, CD4+ T cell, B cell and antibody responses towards SARS-CoV-2 using 7 tetramers and B cell probes in 53 #unvaccinated children and 47 adults from @TheDohertyInst, @MCRI_for_kids, @ChildrensLA, & @StJudeResearch (2/14)

68% of children in our cohort seroconverted at 1 month post COVID-19 infection/exposure which correlated with SARS-CoV-2-specific B cell memory. Thus, most but not all PCR+ children formed antibody responses following infection (3/14)

We used a sensitive tetramer enrichment technique to identify low frequency SARS-CoV-2-specific CD8+ and CD4+ T cell populations directed ex vivo for highly conserved viral epitopes (4/14)

Overall, we found a reduced CD8+ T cell response in children infected with #SARS-CoV-2. Seroconverted children had ~3.9-fold lower ORF1a and N-specific CD8+ T cell responses compared to adults but comparable spike-specific T cell responses (5/14)

Seroconverted children induced strong CD8+ and CD4+ T cell memory responses. However, children had lower CD8+ Tcm & increased Tscm cell populations compared to adults. Exposed individuals who did not seroconvert predominantly expressed a naïve CD8+ & CD4+ T cell phenotype (6/14)

Similar T cell frequencies and phenotypic patterns were observed among #household matched children and their mothers. (7/14)

The #TCR repertoire revealed skewed biases for TRAV and/or TRBV gene segments in seroconverted children and adults, with clonal expansions found in adults but not in children (8/14)

Conclusion 1: Seroconverted children established memory CD8+ & CD4+ T cell responses to conserved SARS-CoV-2 epitopes, which together with cross-reactive antibody responses can potentially protect them from severe COVID-19 when exposed to new variants (9/14)

Conclusion 2: Unknown if children who failed to seroconvert during their first SARS-CoV-2 infection also benefit from rapid viral clearance when encounter new VOC. Our study supports vaccination of children aimed to induce B and T cell memory (10/14)

We thank all our collaborators on this work @louiserowntree, @oanheei, @drlukasz, @melanie_neeland, @LilyAll61591373, @chua_brendon, @HMcQuilten, @Minervina_Asya, @pogorely, @Hyonxhi, @WheatleyAtotheK, @Xiaoxiao_Ivy, @FatimaAmanat,… (11/14)

... @florian_krammer, @ekaitys, @KatieLouFlan, @ppannaraj, @LicciardiLab, @ProfStephenKent, @Jamie_Rossjohn, @PGTimmune, @Shidan_Tosif, @CvandeSandt and @KatherineKedz and those without twitter (12/14)

This study was a multi-institute collaboration between @TheDohertyInst, @UniMelb, @UniMelbMDHS, @MCRI_for_kids, @ChildrensLA, @StJudeResearch, @MonashBDI, @IcahnMountSinai, @UTAS_and many others (13/14)

This study was supported by @nhmrc, @arc_gov_au, @MSCActions, @EU_H2020, @NIH (14/14)