A specific anti-COVID-19 BNT162b2 vaccine-induced early innate immune signature positively correlates with the humoral protective response in healthy and multiple sclerosis vaccine recipients.

Objectives: The very rapidly approved mRNA-based vaccines against SARS-CoV-2 spike glycoprotein, including Pfizer-BioNTech BNT162b2, are effective in protecting from severe coronavirus disease 2019 (COVID-19) in immunocompetent population. However, establishing the duration and identifying correlates of vaccine-induced protection will be crucial to optimise future immunisation strategies. Here, we studied in healthy vaccine recipients and people with multiple sclerosis (pwMS), undergoing different therapies, the regulation of innate immune response by mRNA vaccination in order to correlate it with the magnitude of vaccine-induced protective humoral responses. Methods: Healthy subjects (n = 20) and matched pwMS (n = 22) were longitudinally sampled before and after mRNA vaccination. Peripheral blood mononuclear cell (PBMC)-associated type I and II interferon (IFN)-inducible gene expression, serum innate cytokine/chemokine profile as well as binding and neutralising anti-SARS-COV-2 antibodies (Abs) were measured. Results: We identified an early immune module composed of the IFN-inducible genes Mx1, OAS1 and IRF1, the serum cytokines IL-15, IL-6, TNF-α and IFN-γ and the chemokines IP-10, MCP-1 and MIG, induced 1 day post second and third BNT162b2 vaccine doses, strongly correlating with magnitude of humoral response to vaccination in healthy and MS vaccinees. Moreover, induction of the early immune module was dramatically affected in pwMS treated with fingolimod and ocrelizumab, both groups unable to induce a protective humoral response to COVID-19 vaccine. Conclusion: Overall, this study suggests that the vaccine-induced early regulation of innate immunity is mediated by IFN signalling, impacts on the magnitude of adaptive responses and it might be indicative of vaccine-induced humoral protection.

The zinc proteome of SARS-CoV-2.

Zinc is an essential element for human health. Among its many functions, zinc(II) modulates the immune response to infections and, at high concentrations or in the presence of ionophores, inhibits the replication of various RNA viruses. Structural biology studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed that zinc(II) is the most common metal ion that binds to viral proteins. However, the number of zinc(II)-binding sites identified by experimental methods is far from exhaustive, as metal ions may be lost during protein purification protocols. To better define the zinc(II)-binding proteome of coronavirus, we leveraged the wealth of deposited structural data and state-of-the-art bioinformatics methods. Through this in silico approach, 15 experimental zinc(II) sites were identified and a further 22 were predicted in Spike, open reading frame (ORF)3a/d, ORF8, and several nonstructural proteins, highlighting an essential role of zinc(II) in viral replication. Furthermore, the structural relationships between viral and eukaryotic sites (typically zinc fingers) indicate that SARS-CoV-2 can compete with human proteins for zinc(II) binding. Given the double-edged effect of zinc(II) ions, both essential and toxic to coronavirus, only the complete elucidation of the structural and regulatory zinc(II)-binding sites can guide selective antiviral strategies based on zinc supplementation.

Management of infectious risk of daratumumab therapy in multiple myeloma: A consensus-based position paper from an ad hoc Italian expert panel.

Daratumumab is approved for newly diagnosed or relapsed/refractory multiple myeloma (MM). The use of daratumumab has improved patient outcomes but has changed the frequency and epidemiology of infections. However, the optimal approach to prophylaxis and supportive therapy for daratumumab-emergent infections is unknown and represents an unmet clinical need in MM. Consequently, an expert panel convened to compose recommendations for optimal infection control in patient candidates to or under daratumumab treatment for MM. Scientific evidence on infections secondary to daratumumab was evaluated, and a consensus was developed by group discussion for key questions selected according to the clinical relevance. The following key issues were addressed: infectious risk assessment and risk stratification, infection mitigation strategies, and management of infectious complications in patients with MM treated with daratumumab.

Neutralizing Antibody Responses to SARS-CoV-2 in Recovered COVID-19 Patients Are Variable and Correlate With Disease Severity and Receptor-Binding Domain Recognition

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) caused outbreaks of the pandemic starting from the end of 2019 and, despite ongoing vaccination campaigns, still influences health services and economic factors globally. Understanding immune protection elicited by natural infection is of critical importance for public health policy. This knowledge is instrumental to set scientific parameters for the release of “immunity pass” adopted with different criteria across Europe and other countries and to provide guidelines for the vaccination of COVID-19 recovered patients. Here, we characterized the humoral response triggered by SARS-CoV-2 natural infection by analyzing serum samples from 94 COVID-19 convalescent patients with three serological platforms, including live virus neutralization, pseudovirus neutralization, and ELISA. We found that neutralization potency varies greatly across individuals, is significantly higher in severe patients compared with mild ones, and correlates with both Spike and receptor-binding domain (RBD) recognition. We also show that RBD-targeting antibodies consistently represent only a modest proportion of Spike-specific IgG, suggesting broad specificity of the humoral response in naturally infected individuals. Collectively, this study contributes to the characterization of the humoral immune response in the context of natural SARS-CoV-2 infection, highlighting its variability in terms of neutralization activity, with implications for immune protection in COVID-19 recovered patients.