Humoral and cellular response induced by a second booster of an inactivated SARS-CoV-2 vaccine in adults

The SARS-CoV-2 Omicron variant has challenged the control of the COVID-19 pandemic even in highly vaccinated countries. While a second booster of mRNA vaccines improved the immunity against SARS-CoV-2, the humoral and cellular responses induced by a second booster of an inactivated SARS-CoV-2 vaccine have not been studied. In the context of a phase 3 clinical study, we report that a second booster of CoronaVac® increased the neutralizing response against the ancestral virus yet showed poor neutralization against the Omicron variant. Additionally, isolated PBMCs displayed equivalent activation of specific CD4+ T cells and IFN-γ production when stimulated with a mega-pool of peptides derived from the spike protein of the ancestral virus or the Omicron variant. In conclusion, a second booster dose of CoronaVac® does not improve the neutralizing response against the Omicron variant compared with the first booster dose, yet it helps maintaining a robust spike-specific CD4+ T cell response. ### Competing Interest Statement GZ and WM are SINOVAC Biotech employees and contributed to the conceptualization of the study (clinical protocol and eCRF design) and did not participate in the analysis or interpretation of the data presented in the manuscript. A.S. is a consultant for Gritstone Bio, Flow Pharma, ImmunoScape, Moderna, AstraZeneca, Avalia, Fortress, Repertoire, Gilead, Gerson Lehrman Group, RiverVest, MedaCorp, and Guggenheim. La Jolla Institute for Immunology (LJI) has filed for patent protection for various aspects of T cell epitope and vaccine design work. All other authors declare no conflict of interest. ### Clinical Trial NCT04651790 ### Clinical Protocols ### Funding Statement The CoronaVac03CL Study was funded by The Ministry of Health, Government of Chile, the Confederation of Production and Commerce (CPC), Chile and SINOVAC Biotech. NIH NIAID, under Contract 75N93021C00016, supports AS and Contract 75N9301900065 supports AS, AG and DW. The Millennium Institute on Immunology and Immunotherapy, Agencia Nacional de Investigacion y Desarrollo (ANID) Millennium Science Initiative Program ICN09\_016 / ICN 2021\_045: Millennium Institute on Immunology and Immunotherapy (ICN09\_016 / ICN 2021\_045; former P09/016-F) supports SMB, KA, PAG and AMK; The Innovation Fund for Competitiveness FIC-R 2017 (BIP Code: 30488811-0) supports SMB, PAG and AMK. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Samples analyzed in this study were obtained from volunteers recruited in the clinical trial CoronaVac03CL ([clinicaltrials.gov][1] #[NCT04651790][2]) in Chile (November 2020 to current date). Moreover, the study protocol was reviewed and approved by the Institutional Scientific Ethical Committee of Health Sciences at the Pontificia Universidad Catolica de Chile (#200708006) and the trial was approved by the Chilean Public Health Institute (#24204/20) and conducted according to the current Tripartite Guidelines for Good Clinical Practices, the Declaration of Helsinki, and local regulations. Informed consent was obtained from all volunteers upon enrollment. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript [1]: http://clinicaltrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04651790&atom=%2Fmedrxiv%2Fearly%2F2022%2F08%2F29%2F2022.08.22.22279080.atom