Attitude towards and perception of individual safety after SARS-CoV-2 vaccination among German cancer patients.

PURPOSE: Refusal to receive SARS-CoV-2 vaccination poses a threat to fighting the COVID-19 pandemic. Little is known about German cancer patients' attitude towards and experience with SARS-CoV-2 vaccination. METHODS: Patients were enrolled between 04-11/2021. They completed a baseline questionnaire (BLQ) containing multiple choice questions and Likert items ranging from 1 ("totally disagree") to 11 ("totally agree") regarding their attitude towards vaccination and COVID-19. A follow-up questionnaire (FUQ) was completed after vaccination. RESULTS: 218 patients (43% female) completed BLQ (110 FUQ; 48% female). Most patients agreed to "definitely get vaccinated" (82%) and disagreed with "SARS-CoV-2 vaccination is dispensable due to COVID-19 being no serious threat" (82%; more dissent among men, p = 0.05). Self-assessment as a member of a risk group (p = 0.03) and fear of COVID-19 (p = 0.002) were more common among women. Fear of side effects was more common among women (p = 0.002) and patients with solid or GI tumors (p = 0.03; p < 0.0001). At FUQ, almost all (91%) reported their vaccination to be well tolerated, especially men (p = 0.001). High tolerability correlated with confidence in the vaccine being safe (r = 0.305, p = 0.003). Most patients would agree to get it yearly (78%). After vaccination, patients felt safe meeting friends/family (91%) or shopping (62%). Vacation (32%) or work (22%) were among others considered less safe (less frequent among men, p < 0.05). CONCLUSION: Acceptance of SARS-CoV-2 vaccination is high and it is well tolerated in this sensitive cohort. However, concerns about vaccine safety remain. Those and gender differences need to be addressed. Our results help identify patients that benefit from pre-vaccination consultation.

In-depth analysis of T cell immunity and antibody responses in heterologous prime-boost-boost vaccine regimens against SARS-CoV-2 and Omicron variant.

With the emergence of novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Variants of Concern (VOCs), vaccination studies that elucidate the efficiency and effectiveness of a vaccination campaign are critical to assess the durability and the protective immunity provided by vaccines. SARS-CoV-2 vaccines have been found to induce robust humoral and cell-mediated immunity in individuals vaccinated with homologous vaccination regimens. Recent studies also suggest improved immune response against SARS-CoV-2 when heterologous vaccination strategies are employed. Yet, few data exist on the extent to which heterologous prime-boost-boost vaccinations with two different vaccine platforms have an impact on the T cell-mediated immune responses with a special emphasis on the currently dominantly circulating Omicron strain. In this study, we collected serum and peripheral blood mononuclear cells (PBMCs) from 57 study participants of median 35-year old's working in the health care field, who have received different vaccination regimens. Neutralization assays revealed robust but decreased neutralization of Omicron VOC, including BA.1 and BA.4/5, compared to WT SARS-CoV-2 in all vaccine groups and increased WT SARS-CoV-2 binding and neutralizing antibodies titers in homologous mRNA prime-boost-boost study participants. By investigating cytokine production, we found that homologous and heterologous prime-boost-boost-vaccination induces a robust cytokine response of CD4+ and CD8+ T cells. Collectively, our results indicate robust humoral and T cell mediated immunity against Omicron in homologous and heterologous prime-boost-boost vaccinated study participants, which might serve as a guide for policy decisions.

Impact of SARS-CoV-2 vaccination on systemic immune responses in people living with HIV.

Despite the development of vaccines, which protect healthy people from severe and life-threatening Covid-19, the immunological responses of people with secondary immunodeficiencies to these vaccines remain incompletely understood. Here, we investigated the humoral and cellular immune responses elicited by mRNA-based SARS-CoV-2 vaccines in a cohort of people living with HIV (PLWH) receiving anti-retroviral therapy. While antibody responses in PLWH increased progressively after each vaccination, they were significantly reduced compared to the HIV-negative control group. This was particularly noteworthy for the Delta and Omicron variants. In contrast, CD4+ Th cell responses exhibited a vaccination-dependent increase, which was comparable in both groups. Interestingly, CD4+ T cell activation negatively correlated with the CD4 to CD8 ratio, indicating that low CD4+ T cell numbers do not necessarily interfere with cellular immune responses. Our data demonstrate that despite the lower CD4+ T cell counts SARS-CoV-2 vaccination results in potent cellular immune responses in PLWH. However, the reduced humoral response also provides strong evidence to consider PLWH as vulnerable group and suggests subsequent vaccinations being required to enhance their protection against COVID-19.

Preserved T-cell response in anti-CD20-treated multiple sclerosis patients following SARS-CoV-2 vaccination.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has tremendous implications for the management of patients with autoimmune conditions such as multiple sclerosis (MS) under immune therapies targeting CD20+ B cells (aCD20). Objectives: Here, we investigated humoral and cellular immune responses, including anti-spike titers, neutralization against SARS-CoV-2 wild-type (WT), delta, and omicron variant and T cell responses of aCD20-treated relapsing-remitting MS patients following SARS-CoV-2 vaccination compared with healthy controls. Methods: Blood samples were collected within 4-8 weeks following the second vaccination against SARS-CoV-2. Sera were analyzed for anti-SARS-CoV-2 spike antibodies and neutralization capacity against pseudovirus for wild-type (WT), delta, and omicron variant. Peripheral blood mononuclear cells (PBMCs) were stimulated with a SARS-CoV-2 peptide pool and analyzed via flow cytometry. Results: The aCD20-treated MS patients had lower anti-SARS-CoV-2-spike titers, which correlated with B cell repopulation. Sera of aCD20-treated patients had reduced capacity to neutralize WT, delta, and omicron pseudoviruses in vitro. On the contrary, PBMCs of aCD20-treated patients elicited higher frequencies of CD3+ T cells and CD4+ T cells and comparable response of cytotoxic T cells, while Th1 response was reduced following restimulation with SARS-CoV-2. Conclusion: In summary, aCD20-treated patients have a reduced humoral immune response, depending on B cell repopulation, in accordance with preserved cellular immune response, suggesting partial cellular protection against SARS-CoV-2.

Superior humoral immunity in vaccinated SARS-CoV-2 convalescence as compared to SARS-COV-2 infection or vaccination.

Emerging variants of concern (VOC) raise obstacles in shaping vaccination strategies and ending the pandemic. Vaccinated SARS-CoV-2 convalescence shapes the current immune dynamics. We analyzed the SARS-CoV-2 VOC-specific cellular and humoral response of 57 adults: 42 convalescent mRNA vaccinated patients (C+V+), 8 uninfected mRNA vaccinated (C-V+) and 7 unvaccinated convalescent individuals (C+V-). While C+V+ demonstrated a superior humoral SARS-CoV-2 response against all analyzed VOC (alpha, delta, omicron) compared to C-V+ and C+V-, SARS-CoV-2 reactive CD4+ and CD8+ T cells, which can cross-recognize the alpha, delta and omicron VOC after infection and/or vaccination were observed in all there groups without significant differences between the groups. We observed a preserved cross-reactive C+V+ and C-V+ T cell memory. An inferior humoral response but preserved cross-reactive T cell memory in C+V- compared to C+V+ was observed, as well as an inferior humoral response but preserved cross-reactive T cell memory in C+V- compared to C-V+. Adaptive immunity generated after SARS-CoV-2 infection and vaccination leads to superior humoral immune response against VOC compared to isolated infection or vaccination. Despite the apparent loss of neutralization potential caused by viral evolution, a preserved SARS-CoV-2 reactive T cell response with a robust potential for cross-recognition of the alpha, delta and omicron VOC was detected in all studied cohorts. Our results may have implications on current vaccination strategies.

Immune Response in Moderate to Critical Breakthrough COVID-19 Infection After mRNA Vaccination.

SARS-CoV-2 variants of concern (VOCs) can trigger severe endemic waves and vaccine breakthrough infections (VBI). We analyzed the cellular and humoral immune response in 8 patients infected with the alpha variant, resulting in moderate to fatal COVID-19 disease manifestation, after double mRNA-based anti-SARS-CoV-2 vaccination. In contrast to the uninfected vaccinated control cohort, the diseased individuals had no detectable high-avidity spike (S)-reactive CD4+ and CD8+ T cells against the alpha variant and wild type (WT) at disease onset, whereas a robust CD4+ T-cell response against the N- and M-proteins was generated. Furthermore, a delayed alpha S-reactive high-avidity CD4+ T-cell response was mounted during disease progression. Compared to the vaccinated control donors, these patients also had lower neutralizing antibody titers against the alpha variant at disease onset. The delayed development of alpha S-specific cellular and humoral immunity upon VBI indicates reduced immunogenicity against the S-protein of the alpha VOC, while there was a higher and earlier N- and M-reactive T-cell response. Our findings do not undermine the current vaccination strategies but underline a potential need for the inclusion of VBI patients in alternative vaccination strategies and additional antigenic targets in next-generation SARS-CoV-2 vaccines.