Immunisation efficacy of a stabilised SARS-CoV-2 spike glycoprotein in two geriatric animal models

Age is associated with reduced efficacy of vaccines and linked to higher risk of severe COVID-19. Here we determined the impact of ageing on the efficacy of a SARS-CoV-2 vaccine based on a stabilised Spike glycoprotein (S-29) that had previously shown high efficacy in young animals. Thirteen to 18-m...

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Autores: Usai, Carla|||0000-0002-6373-2765, Ainsua-Enrich, Erola|||0000-0001-7901-5798, Urrea, Víctor|||0000-0002-2577-856X, Pradenas, Edwards|||0000-0001-5162-8920, Lorca-Oró, Cristina|||0000-0001-5351-4169, Tarrés-Freixas, Ferran|||0000-0002-1569-0126, Roca, Núria, Pérez, Mónica, Avila-Nieto, Carlos, Rodriguez de la Concepción, Maria Luisa|||0000-0002-6944-3462, Pedreño López, Núria|||0000-0001-6927-2301, Carabelli, Julieta|||0000-0003-2329-3996, Trinité, Benjamin|||0000-0003-3809-042X, Ballana, Ester|||0000-0002-5215-7363, Riveira Muñoz, Eva|||0000-0002-6396-1162, Izquierdo Useros, Nuria|||0000-0002-1039-1821, Clotet Sala, Bonaventura|||0000-0003-3232-4598, Blanco, Julià|||0000-0002-2225-0217, Guallar, Victor|||0000-0002-4580-1114, Cantero, Guillermo|||0000-0003-4200-503X, Vergara-Alert, Júlia|||0000-0001-7484-444X, Carrillo, Jorge|||0000-0003-0221-5948, Segalés Coma, Joaquim|||0000-0002-1539-7261
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:291295
Acceso en línea:https://ddd.uab.cat/record/291295
https://dx.doi.org/urn:doi:10.1038/s41541-024-00840-0
Access Level:acceso abierto
Palabra clave:Respiratory tract diseases
Experimental models of disease
Descripción
Sumario:Age is associated with reduced efficacy of vaccines and linked to higher risk of severe COVID-19. Here we determined the impact of ageing on the efficacy of a SARS-CoV-2 vaccine based on a stabilised Spike glycoprotein (S-29) that had previously shown high efficacy in young animals. Thirteen to 18-month-old golden Syrian hamsters (GSH) and 22-23-month-old K18-hCAE2 mice were immunised twice with S-29 protein in AddaVax TM adjuvant. GSH were intranasally inoculated with SARS-CoV-2 either two weeks or four months after the booster dose, while all K18-hACE2 mice were intranasally inoculated two weeks after the second immunisation. Body weight and clinical signs were recorded daily post-inoculation. Lesions and viral load were investigated in different target tissues. Immunisation induced seroconversion and production of neutralising antibodies; however, animals were only partially protected from weight loss. We observed a significant reduction in the amount of viral RNA and a faster viral protein clearance in the tissues of immunized animals. Infectious particles showed a faster decay in vaccinated animals while tissue lesion development was not altered. In GSH, the shortest interval between immunisation and inoculation reduced RNA levels in the lungs, while the longest interval was equally effective in reducing RNA in nasal turbinates; viral nucleoprotein amount decreased in both tissues. In mice, immunisation was able to improve the survival of infected animals. Despite the high protection shown in young animals, S-29 efficacy was reduced in the geriatric population. Our research highlights the importance of testing vaccine efficacy in older animals as part of preclinical vaccine evaluation.