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

Carballo-Uicab, G.; Mellado-Sanchez, G.; Gonzalez-Gonzalez, E.; Salinas-Trujano, J.; Mendoza-Salazar, I.; Lopez-Olvera, K.; Gomez-Castellano, K. M.; Salazar, M. I.; Torres-Flores, J. M.; Chagoya-Cortes, H. E.; Paz-De la Rosa, G.; Mena, I.; Rojas-Martinez, O.; Lara-Puente, J. H.; Peralta-Sanchez, G. J.; Sarfati-Mizrahi, D.; Torres-Flores, A.; Sun, W.; Krammer, F.; Garcia-Sastre, A.; Palese, P.; Lopez-Macias, C.; Lozano-Dubernard, B.; Perez-Tapia, S. M.; Almagro, J. C.

doi:10.1101/2025.01.23.634579

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bioRxiv · 10.1101/2025.01.23.634579

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

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global health challenge, causing severe morbidity and mortality, particularly in vulnerable groups such as the elderly, immunocompromised individuals, and those with comorbidities. In low- and middle-income countries (LMICs), vaccine access is hindered by high costs and inequitable distribution. To tackle these issues, Mexico developed the AVX/COVID-12 (V-Wu) vaccine, a recombinant Newcastle disease virus (NDV)-based platform expressing a stabilized ancestral Wuhan spike protein (HexaPro-S). Locally manufactured after rigorous testing and regulatory approval, V-Wu aims to enhance self-sufficiency and equity in immunization. This study evaluates an updated vaccine version, AVX/COVID-12 (V-BA), designed to combat Omicron subvariants by expressing the HexaPro-S protein of 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 analyzed by measuring antibodies against Omicron S proteins BA.2.75.2 and XBB.1.5, as well as neutralizing antibodies against Wuhan, BA.1, XBB.1.16, and JN.1 variants. Both vaccines were safe, eliciting robust antibody responses against Omicron S proteins and neutralizing antibodies against multiple emerging SARS-CoV-2 variants of concern (VOCs). V-BA demonstrated superior protection against current Omicron variants, while V-Wu offered broader coverage, including the ancestral Wuhan strain and emerging variants like JN.1. These findings underscore the adaptability of NDV-based platforms in addressing the evolving SARS-CoV-2 landscape and reaffirm the ongoing utility of the ancestral Patria vaccine. Together, they demonstrate the potential of these platforms to drive the development of next-generation vaccines tailored to emerging viral threats, contributing to global health equity.

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Carballo-Uicab, G., Mellado-Sanchez, G., Gonzalez-Gonzalez, E., Salinas-Trujano, J., Mendoza-Salazar, I., Lopez-Olvera, K., Gomez-Castellano, K. M., Salazar, M. I., Torres-Flores, J. M., Chagoya-Cortes, H. E., Paz-De la Rosa, G., Mena, I., Rojas-Martinez, O., Lara-Puente, J. H., Peralta-Sanchez, G. J., Sarfati-Mizrahi, D., Torres-Flores, A., Sun, W., Krammer, F., Garcia-Sastre, A., Palese, P., Lopez-Macias, C., Lozano-Dubernard, B., Perez-Tapia, S. M., Almagro, J. C.. 2025-01-27. 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. https://doi.org/10.1101/2025.01.23.634579

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