Cross-protection and cross-neutralization capacity of ancestral and VOC-matched SARS-CoV-2 adenoviral vector-based vaccines

• Published in: npj vaccines Vol. 8; no. 1; p. 149
• Main Authors: Vinzón, Sabrina E., Lopez, María V., Cafferata, Eduardo G. A., Soto, Ariadna S., Berguer, Paula M., Vazquez, Luciana, Nusblat, Leonora, Pontoriero, Andrea V., Belotti, Eduardo M., Salvetti, Natalia R., Viale, Diego L., Vilardo, Ariel E., Avaro, Martin M., Benedetti, Estefanía, Russo, Mara L., Dattero, María E., Carobene, Mauricio, Sánchez-Lamas, Maximiliano, Afonso, Jimena, Heitrich, Mauro, Cristófalo, Alejandro E., Otero, Lisandro H., Baumeister, Elsa G., Ortega, Hugo H., Edelstein, Alexis, Podhajcer, Osvaldo L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 04.10.2023; Nature Publishing Group UK; Nature Portfolio
• Subjects: Adenoviruses; COVID-19; COVID-19 vaccines; Immunity (Disease); Neutralization; Rodents; Severe acute respiratory syndrome coronavirus 2; Vaccines
• ISSN: 2059-0105; 2059-0105
• DOI: 10.1038/s41541-023-00737-4

COVID-19 vaccines were originally designed based on the ancestral Spike protein, but immune escape of emergent Variants of Concern (VOC) jeopardized their efficacy, warranting variant-proof vaccines. Here, we used preclinical rodent models to establish the cross-protective and cross-neutralizing capacity of adenoviral-vectored vaccines expressing VOC-matched Spike. CoroVaxG.3-D.FR, matched to Delta Plus Spike, displayed the highest levels of nAb to the matched VOC and mismatched variants. Cross-protection against viral infection in aged K18-hACE2 mice showed dramatic differences among the different vaccines. While Delta-targeted vaccines fully protected mice from a challenge with Gamma, a Gamma-based vaccine offered only partial protection to Delta challenge. Administration of CorovaxG.3-D.FR in a prime/boost regimen showed that a booster was able to increase the neutralizing capacity of the sera against all variants and fully protect aged K18-hACE2 mice against Omicron BA.1, as a BA.1-targeted vaccine did. The neutralizing capacity of the sera diminished in all cases against Omicron BA.2 and BA.5. Altogether, the data demonstrate that a booster with a vaccine based on an antigenically distant variant, such as Delta or BA.1, has the potential to protect from a wider range of SARS-CoV-2 lineages, although careful surveillance of breakthrough infections will help to evaluate combination vaccines targeting antigenically divergent variants yet to emerge.