Newcastle Disease Virus Vector-Based SARS-CoV-2 Vaccine Candidate AVX/COVID-12 Activates T Cells and Is Recognized by Antibodies from COVID-19 Patients and Vaccinated (preprint)

Several effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and implemented in the population. However, the current production capacity falls short of meeting global demand. Therefore, it is crucial to further develop novel vaccine platforms that can bridge the distribution gap. AVX/COVID-12 is a vector-based vaccine that utilizes the Newcastle Disease virus (NDV) to present the SARS-CoV-2 spike protein to the immune system. This study analyses the antigenicity of the vaccine candidate by examining antibody binding and T-cell activation in individuals infected with SARS-CoV-2 or variants of concern (VOCs), as well as in healthy volunteers who received coronavirus disease 2019 (COVID-19) vaccinations. Our findings indicate that the vaccine effectively binds antibodies and activates T-cells in individuals who received 2 or 3 doses of BNT162b2 or AZ/ChAdOx-1-S vaccines. Furthermore, the stimulation of T-cells from patients and vaccine recipients with AVX/COVID-12 resulted in their proliferation and secretion of interferon-gamma (IFN-{gamma}) in both CD4+ and CD8+ T-cells. In conclusion, the AVX/COVID-12 vectored vaccine candidate demonstrates the ability to stimulate robust cellular responses and is recognized by antibodies primed by the spike protein present in SARS-CoV-2 viruses that infected patients, as well as in the mRNA BNT162b2 and AZ/ChAdOx-1-S vaccines. These results support the inclusion of the AVX/COVID-12 vaccine as a booster in vaccination programs aimed at addressing COVID-19 caused by SARS-CoV-2 and its VOCs.

Potential biomarkers for fatal outcome prognosis in a cohort of hospitalized COVID-19 patients with pre-existing co-morbidities (preprint)

Background: The difficulty to predict fatal outcomes in COVID-19 patients, impacts in the general morbidity and mortality due to SARSCoV2 infection, as it wears out the hospital services that care for these patients. Unfortunately, in several of the candidates for prognostic biomarkers proposed, the predictive power is compromised when patients have pre-existing co-morbidities. Methods. A cohort of one hundred and forty-seven patients hospitalized for severe COVID19 was included in a descriptive, observational, single-center, and prospective study. Patients were recruited during the first COVID-19 pandemic wave (April-Nov, 2020). Data were collected from the clinical history while immunophenotyping by multiparameter flow cytometry analysis allowed us to assess the expression of surface markers on peripheral leukocytes. Patients were grouped according to the outcome in survivor or decease. The prognostic value of leukocytes, cytokines or HLA-DR, CD39, and CD73 was calculated. Results: Hypertension and chronic renal failure but not obesity and diabetes were conditions more frequent among the decease group. Mixed hypercitokinemia, including inflammatory(IL-6) and anti-inflammatory(IL-10) cytokines, was more evident in deceased patients. In the decease group, lymphopenia with a higher NLR value was present. HLA-DR expression and the percentage of CD39+ cells were higher than non COVID-19 patients, but remain similar despite outcome. ROC analysis and cut-off value of NLR (69.6%, 9.4), pNLR (71.1%, 13.6), IL-6 (79.7%, 135.2 pg/mL). Conclusion: The expression of HLA-DR, CD39, and CD73, as many serum cytokines (other than IL-6) and chemokines levels do not show prognostic potential compared to NLR and pNLR values.

Seroprevalence and Neutralizing Activity of IgG Antibodies Against SARS-CoV-2 in Mexico (preprint)

Background: Until recently, the incidence of COVID-19 was primarily estimated using molecular diagnostic methods. However, it is internationally accepted that the number of cases is vastly underreported using these methods. Antibody prevalence studies estimate cumulative infection incidences and allow monitoring of transmission dynamics, and the presence of neutralizing antibodies in the population.Methods: In February 2020, the Mexican Social Security Institute began conducting anonymous unrelated sampling of residual sera from specimens collected in clinical laboratories and blood banks across all 32 of the country’s states. Sampling was carried out weekly and began 17 days before Mexico’s first officially confirmed case. The 14,515 sera obtained were analyzed by chemiluminescent-linked immunosorbent assay (CLIA) IgG S1/S2 to determine the presence of total IgG antibodies and, later, positive cases using this technique were also analyzed to determine the rate of neutralization using the enzyme-linked immunosorbent assay (ELISA).Findings: We identified 40 CLIA IgG positive cases before the first official report of SARS-CoV-2 infection in Mexico. The national seroprevalence was 3∙5% in February and 21∙7% in August. Neutralizing activity among patients who generate IgG antibodies was 87∙9% in August 2020 and 10∙4% during the overall study period.Interpretation: The actual extent of the SARS-CoV-2 infection in Mexico is 21 times higher than that reported by molecular techniques. Although the general population is still far from achieving herd immunity, epidemiological indicators of disease burden, and fatality should be re-estimated based on serological studies of this type.Funding Statement: National Council of Science and Technology (CONACyT).Declaration of Interests: The authors have no conflicts of interests to declare.Ethics Approval Statement: This protocol was approved by the scientific, ethics, and biosafety committees of the IMSS National Scientific Research Commission (R-785-2020-60).