T cell immunity is central for the control of viral infections. CoVac-1 is a peptide-based vaccine candidate, composed of SARS-CoV-2 T cell epitopes derived from various viral proteins1,2, combined with the Toll-like receptor 1/2 agonist XS15 emulsified in Montanide ISA51 VG, aiming to induce profound SARS-CoV-2 T cell immunity to combat COVID-19. Here we conducted a phase I open-label trial, recruiting 36 participants aged 18–80 years, who received a single subcutaneous CoVac-1 vaccination. The primary end point was safety analysed until day 56. Immunogenicity in terms of CoVac-1-induced T cell response was analysed as the main secondary end point until day 28 and in the follow-up until month 3. No serious adverse events and no grade 4 adverse events were observed. Expected local granuloma formation was observed in all study participants, whereas systemic reactogenicity was absent or mild. SARS-CoV-2-specific T cell responses targeting multiple vaccine peptides were induced in all study participants, mediated by multifunctional T helper 1 CD4+ and CD8+ T cells. CoVac-1-induced IFNγ T cell responses persisted in the follow-up analyses and surpassed those detected after SARS-CoV-2 infection as well as after vaccination with approved vaccines. Furthermore, vaccine-induced T cell responses were unaffected by current SARS-CoV-2 variants of concern. Together, CoVac-1 showed a favourable safety profile and induced broad, potent and variant of concern-independent T cell responses, supporting the presently ongoing evaluation in a phase II trial for patients with B cell or antibody deficiency.
Against the background of the current COVID‐19 infection dynamics with its rapid spread of SARS‐CoV‐2 variants of concern (VOC), the immunity and the vaccine prevention of healthcare workers (HCWs) against SARS‐CoV‐2 continues to be of high importance. This observational cross‐section study assesses factors influencing the level of anti‐SARS‐CoV‐2‐spike IgG after SARS‐CoV‐2 infection or vaccination. One thousand seven hundred and fifty HCWs were recruited meeting the following inclusion criteria: age ≥18 years, PCR‐confirmed SARS‐CoV‐2 infection convalescence and/or at least one dose of COVID‐19 vaccination. anti‐SARS‐CoV‐2‐spike IgG titers were determined by SERION ELISA agile SARS‐CoV‐2 IgG. Mean anti‐SARS‐CoV‐2‐spike IgG levels increased significantly by number of COVID‐19 vaccinations (92.2 BAU/ml for single, 140.9 BAU/ml for twice and 1144.3 BAU/ml for threefold vaccination). Hybrid COVID‐19 immunized respondents (after infection and vaccination) had significantly higher antibody titers compared with convalescent only HCWs. Anti‐SARS‐CoV‐2‐spike IgG titers declined significantly with time after the second vaccination. Smoking and high age were associated with lower titers. Both recovered and vaccinated HCWs presented a predominantly good humoral immune response. Smoking and higher age limited the humoral SARS‐CoV‐2 immunity, adding to the risk of severe infections within this already health impaired collective.
Seasonal influenza vaccination is established as important infection prevention measure, especially among highly exposed healthcare workers (HCWs) [1]. Coadministration with the third dose of COVID-19 vaccine could be an efficient strategy protecting HCWs from two major viral respiratory infections [2][3][4]. To date, the humoral immunogenicity and side-effects of a coadministered third COVID-19 and a seasonal quadrivalent influenza vaccine are still unclear, and the available data is limited in transferability to the general public [5][6][7]. This preference-based non-randomised controlled study examines the antibody-mediated immunogenicity and vaccine-related side-effects of mRNA-based COVID-19 and seasonal influenza vaccine coadministration in HCWs.1231 participants of the CoVacSer study with two doses of BNT162b2mRNA (30 µg mRNA each) as basic COVID-19 immunisation received a third dose of mRNA-based COVID-19 vaccine administering BNT162b2mRNA (30 µg mRNA) or mRNA-1273 (50 µg mRNA) depending on age and vaccine availability. HCWs could opt for a simultaneous influenza vaccine coadministration (Influvac Tetra vaccine 2021/2022) injected intramuscularly into the opposite arm. HCWs without coadministration received either no seasonal influenza vaccination or at least 14 days apart from the COVID-19 booster. Convalescent HCWs having passed a PCR-confirmed SARS-CoV-2 infection were excluded.Pseudonymised serum blood samples combined with a questionnaire were collected from 1 October 2021 to 31 January 2022 between 14 and 90 days after the COVID-19 vaccination. Anti-SARS-CoV-2-spike IgG levels were obtained using the SERION ELISA agile SARS-CoV-2 IgG (SERION diagnostics, Wuerzburg, Germany) [8].The statistical analyses were performed with R (version 3.1.2) on logarithmised anti-SARS-CoV-2-spike IgG concentrations based on a multiple linear regression analysis. The parameters including potential influencing factors were estimated using a generalised least squares fit (R package nlme) [9,10]. Statistical subgroup differences of the independent categorical variables were calculated with the estimated marginal means. Using the Tukey test statistics, pairwise post hoc tests were performed to expose statistically significant differences. The emmeans package was used to estimate marginal means and to calculate pairwise differences [11]. Investigating the role of side-effects, pairwise Fisher exact tests were performed. To correct against multiple testing, p-values were adjusted using the Benjamini-Yekutielie procedure [12]. Only adjusted p-values below a significance level of 0.05 were considered statistically significant.The study protocol was approved by the ethics committee of the University of Wuerzburg in accordance with the Declaration of Helsinki (file number 79/21). 20.2% (249/1231) of all participants opted for coadministration, whereas 90.4% (225/249) received BNT162b2mRNA and 9.6% (24/249) mRNA-1273 as COVID-19 booster vaccine. 79.8% (982/1231) of all participants were vaccinated with a mRNA-based COVID-19 vacci...
Despite significant progress made in the treatment of patients with multiple myeloma (MM) in the last decade, for patients with early relapse or rapidly progressing high-risk disease, allogeneic hematopoietic stem cell transplantation (SCT) might be an option leading to long-term survival. Here, we retrospectively analyzed the outcomes of 90 MM patients who received allogeneic SCT in our center between 1999 and 2017. We specifically assessed the association of impaired humoral immune reconstitution, referred to as immunoparesis, and post-transplant survival. Sixty-four patients received allogeneic SCT in relapse following 2-7 lines of therapy; 26 patients received upfront tandem autologous-allogeneic SCT. With a median follow-up of 76 months, OS and PFS were 52.6% (95% CI 42.9-64.3) and 36.4% (95% CI 27.6-47.9) at 2 years and 38.6% (95% CI 29.2-51.1) and 25.3% (95% CI 17.5-36.4) at 5 years, respectively. Receiving more than two therapy lines prior to transplantation was an independent risk factor for OS (HR 3.68, 95% CI 2.02-6.70) and PFS (HR 3.69, 95% CI 2.09-6.50). In a landmark analysis at day 200, prolonged immunoparesis was associated with reduced OS (HR 3.22, 95% CI 1.14-9.11). Allogeneic stem cell transplantation offers an additional treatment element that may lead to long-term remission in selected patients with poor prognosis, probably exploiting graft-versus-myeloma effects. Immunoparesis could potentially serve as an indicator for impaired survival following allogeneic transplantation, an observation to be further studied prospectively.
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