The emergence of SARS-CoV-2 variants harboring mutations in the spike (S) protein has raised concern about potential immune escape. Here, we studied humoral and cellular immune responses to wild type SARS-CoV-2 and the B.1.1.7 and B.1.351 variants of concern in a cohort of 121 BNT162b2 mRNA-vaccinated health care workers (HCW). Twenty-three HCW recovered from mild COVID-19 disease and exhibited a recall response with high levels of SARS-CoV-2-specific functional antibodies and virus-specific T cells after a single vaccination. Specific immune responses were also detected in seronegative HCW after one vaccination, but a second dose was required to reach high levels of functional antibodies and cellular immune responses in all individuals. Vaccination-induced antibodies cross-neutralized the variants B.1.1.7 and B.1.351, but the neutralizing capacity and Fc-mediated functionality against B.1.351 was consistently 2- to 4-fold lower than to the homologous virus. In addition, peripheral blood mononuclear cells were stimulated with peptide pools spanning the mutated S regions of B.1.1.7 and B.1.351 to detect cross-reactivity of SARS-CoV-2-specific T cells with variants. Importantly, we observed no differences in CD4+ T-cell activation in response to variant antigens, indicating that the B.1.1.7 and B.1.351 S proteins do not escape T-cell-mediated immunity elicited by the wild type S protein. In conclusion, this study shows that some variants can partially escape humoral immunity induced by SARS-CoV-2 infection or BNT162b2 vaccination, but S-specific CD4+ T-cell activation is not affected by the mutations in the B.1.1.7 and B.1.351 variants.

In July 2022, the ongoing monkeypox (MPX) outbreak was declared a public health emergency of international concern. Modified vaccinia Ankara—Bavarian Nordic (MVA-BN, also known as Imvamune, JYNNEOS or Imvanex) is a third-generation smallpox vaccine that is authorized and in use as a vaccine against MPX. To date, there are no data showing MPX virus (MPXV)-neutralizing antibodies in vaccinated individuals nor vaccine efficacy against MPX. Here we show that MPXV-neutralizing antibodies can be detected after MPXV infection and after historic smallpox vaccination. However, a two-shot MVA-BN immunization series in non-primed individuals yields relatively low levels of MPXV-neutralizing antibodies. Dose-sparing of an MVA-based influenza vaccine leads to lower MPXV-neutralizing antibody levels, whereas a third vaccination with the same MVA-based vaccine significantly boosts the antibody response. As the role of MPXV-neutralizing antibodies as a correlate of protection against disease and transmissibility is currently unclear, we conclude that cohort studies following vaccinated individuals are necessary to assess vaccine efficacy in at-risk populations.

BackgroundSARS-CoV-2 vaccines are highly effective at preventing COVID-19-related morbidity and mortality. As no vaccine is 100% effective, breakthrough infections are expected to occur.MethodsWe analyzed the virological characteristics of 161 vaccine breakthrough infections in a population of 24,706 vaccinated healthcare workers (HCWs), using RT-PCR and virus culture.ResultsThe delta variant (B.1.617.2) was identified in the majority of cases. Despite similar Ct-values, we demonstrate lower probability of infectious virus detection in respiratory samples of vaccinated HCWs with breakthrough infections compared to unvaccinated HCWs with primary SARS-CoV-2 infections. Nevertheless, infectious virus was found in 68.6% of breakthrough infections and Ct-values decreased throughout the first 3 days of illness.ConclusionsWe conclude that rare vaccine breakthrough infections occur, but infectious virus shedding is reduced in these cases.

Rationale: Data on longitudinal recovery after hospitalization for SARS-CoV-2 remain currently scarce, just as outcomes beyond 3 months follow-up. Objective:The aim of the study was to evaluate the sequelae up to 6 months after hospitalization for SARS-CoV-2 infection, considering 1) the recovery of pulmonary function and radiological abnormalities, physical and mental health status, and health-related quality of life (HR-QoL); and 2) the predictors of the most clinically relevant sequelae. Methods:Patients were evaluated at 6 weeks, 3 and 6 months after hospitalization with pulmonary function testing, radiological evaluation, and online questionnaires on physical and mental health status and HR-QoL. Outcomes were analyzed with repeated measurements analyses.Results: Ninety-two patients were included; mean age 58.2±12.3 years, and 58 (63.0%) males. The estimated percentage of patients with impaired FVC improved from 25% at 6 weeks to 11% at 6 months; for impaired diffusion capacity this percentage improved from 63% to 46%.. Radiologically ground glass decreased, but fibrosis persisted. The majority of patients (89.1%) still reported >1 symptom 6 months after discharge. Fatigue decreased significantly over time (p=0.006). Nonetheless, fatigue remained present in 51% of the patients at 6 months. HR-QoL (nearly) normalized in most domains at 6 months, except for physical role functioning, with persistent fatigue and length of hospitalization as most important predictors. Conclusions:During the first 6 months after hospitalization for SARS-CoV-2 most patients demonstrated continuing recovery across all health domains, but persistent sequelae were frequent.Fatigue was the most frequent residual and persisting symptom up to 6 months after hospitalization, importantly impacting HR-QoL.