Postvaccination anti-S IgG levels predict anti-SARS-CoV-2 neutralising activity over 24 weeks in patients with RA.

OBJECTIVES: To correlate immune responses following a two-dose regimen of mRNA anti-SARS-CoV-2 vaccines in patients with rheumatoid arthritis (RA) to the development of a potent neutralising antiviral activity. METHODS: The RECOVER study was a prospective, monocentric study including patients with RA and healthy controls (HCs). Assessments were performed before, and 3, 6, 12 and 24 weeks, after the first vaccine dose, respectively, and included IgG, IgA and IgM responses (against receptor binding domain, S1, S2, N), IFN-γ ELISpots as well as neutralisation assays. RESULTS: In patients with RA, IgG responses developed slower with lower peak titres compared with HC. Potent neutralising activity assessed by a SARS-CoV-2 pseudovirus neutralisation assay after 12 weeks was observed in all 21 HCs, and in 60.3% of 73 patients with RA. A significant correlation between peak anti-S IgG levels 2 weeks after the second vaccine dose and potent neutralising activity against SARS-CoV-2 was observed at weeks 12 and 24. The analysis of IgG, IgA and IgM isotype responses to different viral proteins demonstrated a delay in IgG but not in IgA and IgM responses. T cell responses were comparable in HC and patients with RA but declined earlier in patients with RA. CONCLUSION: In patients with RA, vaccine-induced IgG antibody levels were diminished, while IgA and IgM responses persisted, indicating a delayed isotype switch. Anti-S IgG levels 2 weeks after the second vaccine dose correlate with the development of a potent neutralising activity after 12 and 24 weeks and may allow to identify patients who might benefit from additional vaccine doses or prophylactic regimen.

Insights into coronavirus immunity taught by the murine coronavirus.

Coronaviruses (CoVs) represent enveloped, ss RNA viruses with the ability to infect a range of vertebrates causing mainly lung, CNS, enteric, and hepatic disease. While the infection with human CoV is commonly associated with mild respiratory symptoms, the emergence of SARS-CoV, MERS-CoV, and SARS-CoV-2 highlights the potential for CoVs to cause severe respiratory and systemic disease. The devastating global health burden caused by SARS-CoV-2 has spawned countless studies seeking clinical correlates of disease severity and host susceptibility factors, revealing a complex network of antiviral immune circuits. The mouse hepatitis virus (MHV) is, like SARS-CoV-2, a beta-CoV and is endemic in wild mice. Laboratory MHV strains have been extensively studied to reveal coronavirus virulence factors and elucidate host mechanisms of antiviral immunity. These are reviewed here with the aim to identify translational insights for SARS-CoV-2 learned from murine CoVs.

Development and Immunological Function of Lymph Node Stromal Cells.

Stromal cells have for a long time been viewed as structural cells that support distinct compartments within lymphoid tissues and little more. Instead, an active cross-talk between endothelial and fibroblastic stromal cells drives the maturation of lymphoid niches, a relationship that is recapitulated during lymph node organogenesis, steady-state conditions, and following inflammation. In this review, we go over recent advances in genetic models and high-resolution transcriptomic analyses that have propelled the finer resolution of the stromal cell infrastructure of lymph nodes, revealing that the distinct subsets are strategically positioned to deliver a catered mixture of niche factors to interacting immune cell populations. Moreover, we discuss how changes in the activation state of poised stromal cell-underpinned niches rather than on-demand differentiation of new stromal cell subsets govern the efficient interaction of Ag, APC, and cognate B and T lymphocytes during adaptive immune responses.