Tetravalent SARS-CoV-2 S1 Subunit Protein Vaccination Elicits Robust Humoral and Cellular Immune Responses in SIV-Infected Rhesus Macaque Controllers.

The COVID-19 pandemic has highlighted the need for safe and effective vaccines to be rapidly developed and distributed worldwide, especially considering the emergence of new SARS-CoV-2 variants. Protein subunit vaccines have emerged as a promising approach due to their proven safety record and ability to elicit robust immune responses. In this study, we evaluated the immunogenicity and efficacy of an adjuvanted tetravalent S1 subunit protein COVID-19 vaccine candidate composed of the Wuhan, B.1.1.7 variant, B.1.351 variant, and P.1 variant spike proteins in a nonhuman primate model with controlled SIVsab infection. The vaccine candidate induced both humoral and cellular immune responses, with T- and B cell responses mainly peaking post-boost immunization. The vaccine also elicited neutralizing and cross-reactive antibodies, ACE2 blocking antibodies, and T-cell responses, including spike specific CD4+ T cells. Importantly, the vaccine candidate was able to generate Omicron variant spike binding and ACE2 blocking antibodies without specifically vaccinating with Omicron, suggesting potential broad protection against emerging variants. The tetravalent composition of the vaccine candidate has significant implications for COVID-19 vaccine development and implementation, providing broad antibody responses against numerous SARS-CoV-2 variants.

Agreement of respiratory viruses' detection between nasopharyngeal swab and bronchoalveolar lavage in adults admitted for pneumonia: a retrospective study.

OBJECTIVES: The COVID-19 pandemic has highlighted the high diagnostic accuracy of the nasopharyngeal swab (including in intensive care unit (ICU) patients). This study aimed to compare nasopharyngeal swab and bronchoalveolar lavage (BAL) results for non-SARS-CoV-2 viruses in patients with suspected pneumonia. METHODS: A retrospective analysis was performed in one French academic hospital on consecutive adults from 2012 to 2018 and tested nasopharyngeal swab and BAL within 24 hours by using multiplex PCR. The agreement in pathogen detection between nasopharyngeal swab and BAL was evaluated. RESULTS: Patients were primarily men (n = 178/276, 64.5%), with a median age of 60 years (IQR: 51-68 years). Of the 276 patients, 169 (61%) were admitted to the ICU for acute respiratory distress. We detected at least one respiratory virus in 34.4% of the nasopharyngeal swabs (n = 95/276) and 29.0% of BAL (n = 80/276). Two or more viruses were detected in 2.5% of the nasopharyngeal swabs (n = 7/276) and 2.2% of BAL (n = 6/276). Rhinovirus/enteroviruses were the most frequently detected viral group in 10.2% (n = 29/285) of the nasopharyngeal swabs and 9.5% (n = 27/285) of BAL, followed by influenza A, detected in 5.6% (n = 16/285) of the nasopharyngeal swabs and 4.9% (n = 14/285) of BAL. Overall agreement was 83.7% (n = 231/276 (95% CI [78.7%, 87.7%])) (i.e. same pathogen or pathogen combination was identified in the nasopharyngeal swab and BAL for 231 patients). Rhinovirus/enterovirus (n = 29/231) and respiratory syncytial virus (n = 13/231) had the lowest agreement of 62.1% (n = 18/29 (95% CI [42.4%-78.7%])) and 61.5% (n = 8/13 (95% CI [32.3%-84.9%])), respectively). CONCLUSIONS: There was a good agreement between nasopharyngeal swabs and BAL in detecting respiratory viruses among adult patients with suspected pneumonia. However, these data still encourage BAL in the case of a negative nasopharyngeal swab.

Detection of SARS-CoV-2 N-antigen in blood during acute COVID-19 provides a sensitive new marker and new testing alternatives.

OBJECTIVES: Molecular assays on nasopharyngeal swabs remain the cornerstone of COVID-19 diagnostic. The high technicalities of nasopharyngeal sampling and molecular assays, as well as scarce resources of reagents, limit our testing capabilities. Several strategies failed, to date, to fully alleviate this testing process (e.g. saliva sampling or antigen testing on nasopharyngeal samples). We assessed the clinical performances of SARS-CoV-2 nucleocapsid antigen (N-antigen) ELISA detection in serum or plasma using the COVID-19 Quantigene® (AAZ, France) assay. METHODS: Performances were determined on 63 sera from 63 non-COVID patients and 227 serum samples (165 patients) from the French COVID and CoV-CONTACT cohorts with RT-PCR confirmed SARS-CoV-2 infection, including 142 serum (114 patients) obtained within 14 days after symptoms' onset. RESULTS: Specificity was 98.4% (95% confidence interval [CI], 95.3 to 100). Sensitivity was 79.3% overall (180/227, 95% CI, 74.0 to 84.6) and 93.0% (132/142, 95% CI, 88.7 to 97.2) within 14 days after symptoms onset. 91 included patients had a sera and nasopharyngeal swabs collected in the same 24 hours. Among those with high nasopharyngeal viral loads, i.e. Ct value below 30 and 33, only 1/50 and 4/67 tested negative for N-antigenemia, respectively. Among those with a negative nasopharyngeal RT-PCR, 8/12 presented positive N-antigenemia; the lower respiratory tract was explored for 6 of these 8 patients, showing positive RT-PCR in 5 cases. CONCLUSION: This is the first evaluation of a commercially available serum N-antigen detection assay. It presents a robust specificity and sensitivity within the first 14 days after symptoms onset. This approach provides a valuable new option for COVID-19 diagnosis, only requiring a blood draw and easily scalable in all clinical laboratories.