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

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-γ) 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. ### Competing Interest Statement The vaccine candidate used in this study was developed by faculty members at the Icahn School of Medicine at Mount Sinai including P.P., F.K. and A.G.-S. Mount Sinai is seeking to commercialize this vaccine; therefore, the institution and its faculty inventors could benefit financially. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-849 CoV-2 serological assays (USA Provisional Application Numbers: 62/994,252, 63/018,457, 63/020,503 and 63/024,436) and NDV-based SARS-CoV-2 vaccines (USA Provisional Application Number: 63/251,020) which list F.K. as co-inventor. A.G.-S. and P.P. are a co-inventor in the NDV-based SARS-CoV-2 vaccine patent application. Patent applications were submitted by the Icahn School of Medicine at Mount Sinai. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2 and another company, CastleVax, to commercialize SARS-CoV-2 vaccines. F.K., P.P. and A.G.-S. serve on the scientific advisory board of CastleVax and are listed as co-founders of the company. F.K. has consulted for Merck, Seqirus, Curevac, and Pfizer, and is currently consulting for Gritstone, Third Rock Ventures, GSK, and Avimex. The F.K. laboratory has been collaborating with Pfizer on animal models of SARS-CoV-2. The A.G.-S. laboratory has received research support from GSK, Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapeutics, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories and Merck. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Synairgen, Paratus, Pfizer and Prosetta. A.G.-S. has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott, and AstraZeneca. P.P. has a consulting agreement with Avimex. The live vaccine used in the study was developed by members of Avimex. Avimex filed patent applications with Mount Sinai and CONAHCYT. M.T., D.S.-M., C.L.-M., H.E.C.-C., F.C.-P., G.P.D.L., and B.L.-D. are named as inventors on at least one of those patent applications. The rest of the participants are employees of their corresponding institutions and declare no competing interests.