Addressing SARS-CoV-2 Evolution: Neutralization of Emerging Variants of Concern by the AVX/COVID-12 'Patria' Vaccine Based on HexaPro-S Ancestral Wuhan Spike or Its Updated BA.2.75.2 Version

Gregorio Carballo-Uicab^1,2,3Gabriela Mellado-Sanchez^1,2Edith González-González^1,2Juana Salinas-Trujano^1,2Ivette Mendoza-Salazar^1,2,3Karina López-Olvera^1,2Keyla María Gómez-Castellano^1,2Ma. Isabel Salazar⁴Jesus Miguel Torres Flores⁴Héctor Elías Chagoya-Cortés⁵Georgina Paz-De la Rosa⁶Ignacio Mena⁶Oscar Rojas-Martínez⁶Jesús Horacio Lara-Puente⁶Gustavo Javier Peralta-Sánchez⁶David Sarfati-Mizrahi⁶Alejandro Torres-Flores^3,7Weina Sun⁸Florian Krammer^10,11,8,9Adolfo García-Sastre^{12,13,14,15,8,9}Peter Palese⁸Constantino López-Macías⁷Bernardo Lozano-Dubernard⁶Sonia M. Pérez-Tapia^1,2,3*Juan C Almagro^1,16,2*

• ¹Unidad de Desarrollo e Investigación en Bioprocesos, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico, Mexico
• ²Laboratorio Nacional para Servicios Especializados de Investigación, Desarrollo e Innovación (I+D+i) para Farmoquímicos y Biotecnológicos, LANSEIDI-FarBiotec-CONACyT, Mexico City, México, Mexico
• ³Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico, Mexico
• ⁴Laboratorio Nacional de Vacunología y Virus Tropicales (LNVyVT), Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico city, Mexico
• ⁵Consultora Mextrategy, S.A.S. de C.V., Mexico city, Mexico
• ⁶Laboratorio Avi-Mex, S.A. de C.V. (Avimex), Mexico city, Mexico
• ⁷Unidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico city, Mexico
• ⁸Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States
• ⁹Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States
• ¹⁰Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, New York, United States
• ¹¹Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, Vienna, Austria
• ¹²Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States
• ¹³Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States
• ¹⁴The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States
• ¹⁵The Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, United States
• ¹⁶CTI-Boston, GlobalBio Inc, Cambridge, 02115, United States

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global health challenge, causing severe morbidity and mortality, particularly among vulnerable populations such as the elderly, immunocompromised individuals, and those with comorbidities. In low-and middle-income countries (LMICs), vaccine access is often limited due to high costs and inequitable distribution. To address these challenges, Mexico developed AVX/COVID-12 (V-Wu), a recombinant Newcastle disease virus (NDV)-based vaccine expressing a stabilized ancestral Wuhan spike protein (HexaPro-S). Locally produced following rigorous testing and regulatory approval, V-Wu aims to enhance self-sufficiency and equitable immunization. This study evaluates an updated vaccine version, AVX/COVID-12 (V-BA), engineered to counter Omicron subvariants by expressing the HexaPro-S protein from BA.2.75.2. Both vaccines were administered intramuscularly in K18-hACE2 transgenic and BALB/c mouse models using a prime-boost regimen. Immunogenicity was assessed by quantifying binding antibodies against Omicron S proteins (BA.2.75.2 and XBB.1.5) and neutralizing antibodies against multiple variants, including Wuhan, BA.1, XBB.1.16, and JN.1. Both vaccines were safe and elicited robust antibody responses against Omicron S proteins and neutralizing activity against emerging SARS-CoV-2 variants of concern (VOCs). V-BA demonstrated superior neutralizing activity against current Omicron variants, while V-Wu offered broader cross-reactivity, including the ancestral Wuhan strain and emerging variants like JN.1. These findings highlight the adaptability of NDV-based vaccine platforms to the evolving SARS-CoV-2 landscape and reaffirm the continued relevance of the ancestral Patria vaccine. Collectively, they underscore the potential of these platforms to support the development of next-generation vaccines tailored to emerging viral threats, contributing to global health equity.