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Background: The global inequity in the distribution of COVID-19 vaccines underscores the urgent need for innovative and cost-effective vaccine technologies to address access disparities and implement local manufacturing capabilities. This is essential for achieving and sustaining widespread immunity, and for ensuring timely protection of vulnerable populations during future booster campaigns in lower- middle income countries (LMICs)., Methods: To address this need, we conducted a phase II clinical trial to evaluate the safety and immunogenicity of the locally manufactured AVX/COVID-12 "Patria" (AVX) vaccine as a booster dose. The vaccine was administered either intramuscularly (IM) or intranasally (IN) to participants who had previously completed a vaccination regimen for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using adenoviral vector, inactivated virus, or mRNA-based vaccines. Participants with initial anti-spike IgG titers below 1,200 U/mL were included, allowing us to observe the booster effect induced by vaccination., Results: Both IM and IN immunization with AVX were found to be safe and well-tolerated. The vaccine induced a significant (>2.5-fold) increase in neutralizing antibodies against the ancestral Wuhan strain and variants of concern (VOCs), including Alpha, Beta, Delta, and Omicron (BA.2 and BA.5). This immune response was further supported by increased cellular production of interferon-gamma (IFN-γ), demonstrating a robust and multifaceted immune reaction., Conclusions: The administration of AVX as a booster dose, whether through IM or IN routes, was safe and well-tolerated. The vaccine extended immune responses not only against the ancestral Wuhan-1 strain but also against various VOCs. Its ability to enhance preexisting immune responses suggests a potential contribution to expanding and sustaining herd immunity within the population., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Laboratorios Avimex S.A. de C.V. reports financial support was provided by Consejo Nacional de Humanidades, Ciencia y Tecnología. México. Bernardo Lozano-Dubernard reports financial support was provided by Laboratorios Avimex S.A. de C.V. P.P., F.K., and A.G.-S. has patent #62/994,252 pending to Mount Sinai. P.P., F.K., and A.G.-S. has patent #63/018,457 pending to Mount Sinai. P.P., F.K., and A.G.-S. has patent #63/020,503 pending to Mount Sinai. P.P., F.K., and A.G.-S. has patent #63/024,436 pending to Mount Sinai. P.P., F.K., and A.G.-S. has patent #63/251,020 pending to Mount Sinai. M.T., D.S.-M., C.L.-M., H.E.C.-C., F.C.-P., G.P.D.L., and B.L.-D. has patent #PCT/IB2022/058886. MX/a/2021/011439 pending to Avimex S.A. de C.V. The vaccine candidate administered 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 co-inventors 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. C.L.-M. has consulted for AstraZeneca. 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. PP has a consulting agreement with Avimex. Members of Avimex developed the live vaccine used in this study. 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 clinical study was entirely performed in Mexico, and Mount Sinai had no role in it. The rest of the participants are employees of their corresponding institutions and declare no competing interests. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: 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., Methods: This study aims to analyze 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., Results: 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., Discussion: 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 Interests: Author HC-C was employed by company Consultora Mextrategy. Authors GP-DR, OR-M, AS-M, GP-S, DS-M and BL-D were employed by company Laboratorio Avi-Mex S.A. de C.V. The vaccine candidate administered in this study was developed by faculty members at the Icahn School of Medicine at Mount Sinai including PP, FK and AG-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 FK as co-inventor. AG-S and PP 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. FK, PP and AG-S serve on the scientific advisory board of CastleVax and are listed as co-founders of the company. FK has consulted for Merck, Seqirus, Curevac, and Pfizer, and is currently consulting for Gritstone, Third Rock Ventures, GSK, and Avimex. The FK laboratory has been collaborating with Pfizer on animal models of SARS-CoV-2. The AG-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. AG-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. AG-S has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott, and AstraZeneca. PP 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. DS-M, CL-M, HC-C, GP-D, and BL-D are named as inventors on at least one of those patent applications. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Laboratorio Avi-Mex S.A. de C.V., project number R-2021-785-048. The funder had the following involvement in the study: resources, writing – review and editing, conceptualization, supervision, and validation. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Torres-Flores, Ontiveros-Padilla, Madera-Sandoval, Tepale-Segura, Gajón-Martínez, Rivera-Hernández, Ferat-Osorio, Cérbulo-Vázquez, Arriaga-Pizano, Bonifaz, Paz-De la Rosa, Rojas-Martínez, Suárez-Martínez, Peralta-Sánchez, Sarfati-Mizrahi, Sun, Chagoya-Cortés, Palese, Krammer, García-Sastre, Lozano-Dubernard and López-Macías.)

There is still a need for safe, efficient, and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at a low cost, similar to influenza virus vaccines, and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open-label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety, and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe, and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737., (© 2023. The Author(s).)