Current studies focus on cellular and humoral immunity induced by novel SARS-CoV-2 vaccines. Non-responders to vaccinations are not uncommonly encountered in clinical medicine (e.g. in the field of hepatitis B). Whereas vaccine-induced humoral immunity against SARS-CoV-2 is compromised by emerging Variants of Concern (VOCs), cellular immunity against SARS-CoV-2 is emerging as resilient against VOCs. Thus commercially available test kits for diagnostic laboratories designed to evaluate cellular immune responses to SARS-CoV-2 are urgently needed. Here we evaluated the novel QuantiFERON SARS-CoV-2 assay (Qiagen) measuring INF-ɣ release induced by two spike-derived peptide pools (Ag1 and Ag2) in a cohort of health care workers vaccinated with the mRNA-1273 vaccine and confirmed humoral response. Our study indicates the usefulness of this novel assay for routine laboratories to evaluate cellular immunity against SARS-CoV-2 in response to mRNA-1273 vaccination.

Background Due to large vaccination efforts with novel vaccines there is an increasing need for laboratory tests assessing successful immunizations with SARS-CoV-2 vaccines. Unfortunately classical neutralization assays are laborious, time-consuming and require an adequate biosafety level laboratory. Recently, convenient ELISA-based surrogate neutralization assays (sVNTs) for determination of neutralizing SARS-CoV-2 antibodies have been developed. Study Design Our study compares the two novel ELISA-based SARS-CoV-2 surrogate neutralization assays “cPass SARS-CoV-2 Surrogate Virus Neutralization Test Kit” (GenScript Biotech, USA) and the “TECO SARS-CoV-2 Neutralization Antibody Assay” (TECOmedical, Switzerland) using 93 sera drawn from health care workers (HCVs) 2-3 weeks following the second vaccination with mRNA-1273 and 40 control sera from the pre-SARS-CoV-2 era before 2019 Results We found a sensitivity of 100% and 91,4% and a specificity of 100% and 100% for the GenScript assay and the TECO assay, respectively. Both sVNTs show a high correlation with anti-S IgG. Moreover, both sVNTs correlate well with each other. Conclusions Surrogate neutralization assays based on the RBD as bait feature a high specificity and sensitivity for identifying humoral neutralizing activity in individuals vaccinated with the spike-based vaccine mRNA-1273. Although these assays appear well-suited for confirming successful vaccinations with spike-based vaccines, additional studies should compare both assays regarding other purposes such as screening COVID-recovered patients or individuals vaccinated with inactivated whole virus vaccines.

ObjectiveThe study aim was to evaluate a small low-field NMR (nuclear magnetic resonance) scanner, the NMR-MOUSE®, for detecting changes in intestinal diffusion under different (patho-) physiological perfusion states.MethodsLaparotomy was performed on 8 female landrace pigs (body weight 70±6 kg) and the feeding vessels of several intestinal loops were dissected. Successively, the intestinal loops were examined using O2C (oxygen to see, LEA Medizintechnik GmbH, Giessen, Germany) for microcirculatory monitoring and the NMR-MOUSE® for diffusion measurement (fast and slow components). On each loop the baseline measurement (physiological perfusion) was followed by one of the following main procedures: method 1 –ischemia; method 2 –flow reduction; method 3 –intraluminal glucose followed by ischemia; method 4 –intraluminal glucose followed by flow reduction. Additionally, standard perioperative monitoring (blood pressure, ECG, blood gas analyses) and histological assessment of intestinal biopsies was performed.ResultsThere was no statistical overall time and method effect in the NMR-MOUSE measurement (fast component: ptime = 0.6368, pmethod = 0.9766, slow component: ptime = 0.8216, pmethod = 0.7863). Yet, the fast component of the NMR-MOUSE measurement showed contrary trends during ischemia (increase) versus flow reduction (decrease). The slow-to-fast diffusion ratio shifted slightly towards slow diffusion during flow reduction. The O2C measurement showed a significant decrease of oxygen saturation and microcirculatory blood flow during ischemia and flow reduction (p < .0001). The local microcirculatory blood amount (rHb) showed a significant mucosal increase (pClamping(method 1) = 0.0007, pClamping(method 3) = 0.0119), but a serosal decrease (pClamping(method 1) = 0.0119, pClamping(method 3) = 0.0078) during ischemia. The histopathological damage was significantly higher with increasing experimental duration and at the end of methods 3 and 4 (p < .0001,Fisher-test).ConclusionMonitoring intestinal diffusion changes due to different perfusion states using the NMR-MOUSE is feasible under experimental conditions. Despite the lack of statistical significance, this technique reflects perfusion changes and therefore seems promising for the evaluation of different intestinal perfusion states in the future. Beforehand however, an optimization of this technology, including the optimization of the penetration depth, as well as further validation studies under physiological conditions and including older animals are required.

Knowledge about mRNA-1273 elicited T-cell response is limited. We investigated adverse reactions and interferon gamma release by specific T-cells among mRNA-1273 vaccinated health care workers. Seven to 13 weeks after complete vaccination low levels of specific T-cells were detected not correlating with antibody response. Severity of symptoms after first and number of symptoms after second immunization were associated with T-cell response. Assessment of T-cell response in addition to antibody response is crucial because even few specific T-cells could add to protection against infection. Investigation of mRNA-1273 induced inflammatory processes might help improve reactogenicity and immunogenicity.