Kleio-Maria Verrou

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Background: Preterm infants mount lower humoral responses to the 13-valent pneumococcal conjugate vaccine (PCV13) than full-term infants; however, the long-term impact of prematurity on vaccine-induced protection remains unclear. This study investigates the innate and adaptive immune responses to PCV13 in preterm versus full-term infants. Methods: Thirty-eight infants (19 preterm, 19 full-term) received PCV13 at 2, 4, 6, and 12 months. Polysaccharide-specific memory B cells (MBCs) were enumerated and phenotyped by flow cytometry, while PS-specific IgG concentrations were measured by ELISA before and after the third and booster doses. RNA sequencing was performed before and 3 days after the third dose. Results: Primary immunization induced a markedly broader, predominantly proinflammatory transcriptional response in preterm infants. Preterm infants exhibited higher frequencies of total and PS-specific extragerminal center (GC) MBCs but lower switched MBCs following primary immunization; these differences largely converged postbooster. Polysaccharide-specific IgG titers remained generally lower in preterm infants. Polysaccharide-specific switched MBCs postprimary correlated positively with antibody titers postbooster. The broad upregulation of proinflammatory genes in preterm infants was negatively correlated with antibody concentrations. Conclusions: PCV13 immunization elicits distinct immunological profiles in preterm versus full-term infants. Booster immunization largely harmonized MBC composition across gestational groups, while early GC-derived MBC populations emerged as candidate correlates of durable immunity.

Background: mRNA vaccines have played a crucial role in controlling the SARS-CoV-2 global pandemic. However, the immunological mechanisms involved in the induction, magnitude and longevity of mRNA-vaccine-induced protective immunity are still unclear. Methods: In our study, we used whole-RNA sequencing along with detailed immunophenotyping of antigen-specific T cells and humoral RBD-specific response to dual immunization with the Pfizer–BioNTech mRNA vaccine (BNT162b2) and correlated them with response to an additional dose, administered 10 months later, in order to comprehensively profile the immune response of healthy volunteers to BNT162b2. Results: Primary dual immunization induced upregulation of the Type I interferon pathway and generated spike protein (S)-specific IFN-γ+ and TNF-α+ CD4 T cells, S-specific memory CD4 T cells, and RBD-specific antibodies against SARS-CoV-2. S-specific CD4 T cells induced by the primary series correlated with the RBD-specific antibody titers to a third dose. Conclusions: This study demonstrates the induction of both innate and adaptive immunity in response to the BNT162b2 mRNA vaccine in a coordinated manner and identifies the central role of primarily induced CD4+ T cells as a predictive biomarker of the magnitude of anamnestic immune response.

A key unknown of the functional space in tumor immunity is whether CD4 T cells depend on intratumoral MHCII cancer antigen recognition. MHCII-expressing, antigen-presenting cancer-associated fibroblasts (apCAFs) have been found in breast and pancreatic tumors and are considered to be immunosuppressive. This analysis shows that antigen-presenting fibroblasts are frequent in human lung non-small cell carcinomas, where they seem to actively promote rather than suppress MHCII immunity. Lung apCAFs directly activated the TCRs of effector CD4 T cells and at the same time produced C1q, which acted on T cell C1qbp to rescue them from apoptosis. Fibroblast-specific MHCII or C1q deletion impaired CD4 T cell immunity and accelerated tumor growth, while inducing C1qbp in adoptively transferred CD4 T cells expanded their numbers and reduced tumors. Collectively, we have characterized in the lungs a subset of antigen-presenting fibroblasts with tumor-suppressive properties and propose that cancer immunotherapies might be strongly dependent on in situ MHCII antigen presentation.