Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study.

BACKGROUND: Heterologous vaccine regimens have been widely discussed as a way to mitigate intermittent supply shortages and to improve immunogenicity and safety of COVID-19 vaccines. We aimed to assess the reactogenicity and immunogenicity of heterologous immunisations with ChAdOx1 nCov-19 (AstraZeneca, Cambridge, UK) and BNT162b2 (Pfizer-BioNtech, Mainz, Germany) compared with homologous BNT162b2 and ChAdOx1 nCov-19 immunisation. METHODS: This is an interim analysis of a prospective observational cohort study enrolling health-care workers in Berlin (Germany) who received either homologous ChAdOx1 nCov-19 or heterologous ChAdOx1 nCov-19-BNT162b2 vaccination with a 10-12-week vaccine interval or homologous BNT162b2 vaccination with a 3-week vaccine interval. We assessed reactogenicity after the first and second vaccination by use of electronic questionnaires on days 1, 3, 5, and 7. Immunogenicity was measured by the presence of SARS-CoV-2-specific antibodies (full spike-IgG, S1-IgG, and RBD-IgG), by an RBD-ACE2 binding inhibition assay (surrogate SARS-CoV-2 virus neutralisation test), a pseudovirus neutralisation assay against two variants of concerns (alpha [B.1.1.7] and beta [B.1.351]), and anti-S1-IgG avidity. T-cell reactivity was measured by IFN-γ release assay. FINDINGS: Between Dec 27, 2020, and June 14, 2021, 380 participants were enrolled in the study, with 174 receiving homologous BNT162b2 vaccination, 38 receiving homologous ChAdOx1 nCov-19 vaccination, and 104 receiving ChAdOx1 nCov-19-BNT162b2 vaccination. Systemic symptoms were reported by 103 (65%, 95% CI 57·1-71·8) of 159 recipients of homologous BNT162b2, 14 (39%, 24·8-55·1) of 36 recipients of homologous ChAdOx1 nCov-19, and 51 (49%, 39·6-58·5) of 104 recipients of ChAdOx1 nCov-19-BNT162b2 after the booster immunisation. Median anti-RBD IgG levels 3 weeks after boost immunisation were 5·4 signal to cutoff ratio (S/co; IQR 4·8-5·9) in recipients of homologous BNT162b2, 4·9 S/co (4·3-5·6) in recipients of homologous ChAdOx1 nCov-19, and 5·6 S/co (5·1-6·1) in recipients of ChAdOx1 nCov-19- BNT162b2. Geometric mean of 50% inhibitory dose against alpha and beta variants were highest in recipients of ChAdOx1 nCov-19-BNT162b2 (956·6, 95% CI 835·6-1095, against alpha and 417·1, 349·3-498·2, against beta) compared with those in recipients of homologous ChAdOx1 nCov-19 (212·5, 131·2-344·4, against alpha and 48·5, 28·4-82·8, against beta; both p<0·0001) or homologous BNT162b2 (369·2, 310·7-438·6, against alpha and 72·4, 60·5-86·5, against beta; both p<0·0001). SARS-CoV-2 S1 T-cell reactivity 3 weeks after boost immunisation was highest in recipients of ChAdOx1 nCov-19-BNT162b2 (median IFN-γ concentration 4762 mIU/mL, IQR 2723-8403) compared with that in recipients of homologous ChAdOx1 nCov-19 (1061 mIU/mL, 599-2274, p<0·0001) and homologous BNT162b2 (2026 mIU/mL, 1459-4621, p=0·0008) vaccination. INTERPRETATION: The heterologous ChAdOx1 nCov-19-BNT162b2 immunisation with 10-12-week interval, recommended in Germany, is well tolerated and improves immunogenicity compared with homologous ChAdOx1 nCov-19 vaccination with 10-12-week interval and BNT162b2 vaccination with 3-week interval. Heterologous prime-boost immunisation strategies for COVID-19 might be generally applicable. FUNDING: Forschungsnetzwerk der Universitätsmedizin zu COVID-19, the German Ministry of Education and Research, Zalando SE.

Comparison of seven commercial SARS-CoV-2 rapid point-of-care antigen tests: a single-centre laboratory evaluation study.

BACKGROUND: Antigen point-of-care tests (AgPOCTs) can accelerate SARS-CoV-2 testing. As some AgPOCTs have become available, interest is growing in their utility and performance. Here we aimed to compare the analytical sensitivity and specificity of seven commercially available AgPOCT devices. METHODS: In a single-centre, laboratory evaluation study, we compared AgPOCT products from seven suppliers: the Abbott Panbio COVID-19 Ag Rapid Test, the RapiGEN BIOCREDIT COVID-19 Ag, the Healgen Coronavirus Ag Rapid Test Cassette (Swab), the Coris BioConcept COVID-19 Ag Respi-Strip, the R-Biopharm RIDA QUICK SARS-CoV-2 Antigen, the nal von minden NADAL COVID-19 Ag Test, and the Roche-SD Biosensor SARS-CoV Rapid Antigen Test. Tests were evaluated on recombinant SARS-CoV-2 nucleoprotein, cultured endemic and emerging coronaviruses, stored respiratory samples with known SARS-CoV-2 viral loads, stored samples from patients with respiratory pathogens other than SARS-CoV-2, and self-sampled swabs from healthy volunteers. We estimated analytical sensitivity in terms of approximate viral concentrations (quantified by real-time RT-PCR) that yielded positive AgPOCT results, and specificity in terms of propensity to generate false-positive results. FINDINGS: In 138 clinical samples with quantified SARS-CoV-2 viral load, the 95% limit of detection (concentration at which 95% of test results were positive) in six of seven AgPOCT products ranged between 2·07 × 106 and 2·86 × 107 copies per swab, with an outlier (RapiGEN) at 1·57 × 1010 copies per swab. The assays showed no cross-reactivity towards cell culture or tissue culture supernatants containing any of the four endemic human coronaviruses (HCoV­229E, HCoV­NL63, HCoV­OC43, or HCoV­HKU1) or MERS-CoV, with the exception of the Healgen assay in one repeat test on HCoV-HKU1 supernatant. SARS-CoV was cross-detected by all assays. Cumulative specificities among stored clinical samples with non-SARS-CoV-2 infections (n=100) and self-samples from healthy volunteers (n=35; cumulative sample n=135) ranged between 98·5% (95% CI 94·2-99·7) and 100·0% (97·2-100·0) in five products, with two outliers at 94·8% (89·2-97·7; R-Biopharm) and 88·9% (82·1-93·4; Healgen). False-positive results did not appear to be associated with any specific respiratory pathogen. INTERPRETATION: The sensitivity range of most AgPOCTs overlaps with SARS-CoV-2 viral loads typically observed in the first week of symptoms, which marks the infectious period in most patients. The AgPOCTs with limit of detections that approximate virus concentrations at which patients are infectious might enable shortcuts in decision making in various areas of health care and public health. FUNDING: EU's Horizon 2020 research and innovation programme, German Ministry of Research, German Federal Ministry for Economic Affairs and Energy, German Ministry of Health, and Bill & Melinda Gates Foundation.

Pre-emptive genomic surveillance of emerging ebolaviruses.

Genomic surveillance during ebolavirus outbreaks to elucidate transmission chains and develop diagnostic tests is delayed by the laborious development of variant-specific laboratory assays. We developed a new protocol combining 31 parallel PCR assays with Illumina/MinION-based sequencing, allowing generic ebolavirus genomic surveillance, validated using cell culture-derived Ebola, Reston, Sudan and Taï Forest virus at concentrations compatible with patient viral loads. Our approach enables pre-emptive genomic surveillance of ongoing and future ebolavirus outbreaks irrespective of variant divergence.