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

AgeisassociatedwithreducedefficacyofvaccinesandlinkedtohigherriskofsevereCOVID-19.Herewe 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 AddaVaxTM 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 RNAinnasalturbinates; viral nucleoprotein amount decreased in both tissues. Inmice, 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 high lights the importance of testing vaccine efficacy in older animals as part of preclinical vaccine evaluation.

This work was partly supported by Grifols pharmaceutical, the CERCA Program (2021 SGR 00452; Generalitat de Catalunya), Direcció General de Recerca i Innovació en Salut (Generalitat de Catalunya) (projects SLD0015 and SLD0016), the Carlos III Health Institute (PI17/01518 and PI18/01332), and the crowdfunding projects “YomeCorono”, BonPreu/Esclat, and Correos. JB is supported by the Health Department of the Catalan Government (Generalitat de Catalunya). CAN was supported by predoctoral grants from Generalitat de Catalunya (2020 FI_B_0742; 2022 FI_B_00698). EPwas supportedbyadoctoralgrant from the National Agency for Research and Development of Chile (ANID: 72180406). NIU is supported by the Spanish Ministry of Science and Innovation (grant PID2020-117145RB-I00), EU HORIZON-HLTH-2021-CORONA-01 (grant 101046118). This study was also supported by CIBER - Consorcio Centro de Investigación Biomédica en Red (CB 2021), Carlos III Health Institute, Ministerio de Ciencia e Innovación and Unión Europea – NextGenerationEU. Funders had no role in study design, data analysis, decision to publish, or manuscript preparation. We would like to thank Foundation Dormeur that support the acquisition of the QuantStudio-5 real-time PCR system, an Eclipse Ts2R-FL Inverted Research Microscope and an ÄKTA Go protein purification system. Graphical abstract and drawing in Figs. 1 and 4 were created with BioRender.com.

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