Chalerm Liwsrisakun,1* Supansa Pata,2,3* Witida Laopajon,2,3* Nuchjira Takheaw,2,3 Warawut Chaiwong,1 Pilaiporn Duangjit,1 Juthamas Inchai,1 Kantinan Chuensirikulchai,2,3 Passaworn Cheyasawan,3 Chaicharn Pothirat,1 Chaiwat Bumroongkit,1 Athavudh Deesomchok,1 Theerakorn Theerakittikul,1 Atikun Limsukon,1 Pattraporn Tajarernmuang,1 Nutchanok Niyatiwatchanchai,1 Konlawij Trongtrakul,1 Watchara Kasinrerk,2,3

Affiliations:
1 Division of Pulmonary, Critical Care, and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
2 Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
3 Biomedical Technology Research Center, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency at the Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand

*Chalerm Liwsrisakun, Supansa Pata, Witida Laopajon contributed equally to this work., PhD

Abstract

Background: The concept of heterologous vaccination against SARS-CoV-2 infection has been adopted in Thailand with limited data on the induction of humoral and cellular immunity, particularly the CoronaVac/ChAdOx-1 (CoVac/ChAd) regimen in the elderly.
Objectives: In this study, the immune responses of the elderly induced by heterologous CoVac/ChAd and homologous ChAdOx-1 (ChAd/ChAd) vaccinations were demonstrated.
Methods: A prospective observational study involving healthy participants aged ≥ 60 years who received heterologous CoVac/ChAd or homologous ChAd/ChAd vaccination was conducted. Surrogate neutralizing antibody (NAb) and T-cell responses against the SARS-CoV-2 wild type (WT) and variants of concern were determined at pre and post vaccinations.
Results: At 4 and 12 weeks after heterologous or homologous vaccination, the NAb levels against WT, Alpha, Beta, and Delta variants between each group were not significantly different, except for significant lower NAb against the Beta variant in heterologous group at 12 weeks after vaccination. The NAb against the Omicron at 4 weeks post-vaccination were below the cutoff level for antibody detection in both groups. However, higher spike-specific CD4 T cell producing IFN-γ and TNF-α in the heterologous than the homologous vaccination were observed. Insignificant difference of cellular immune responses to spike-peptides of Alpha, Beta, and Delta variants and their WT homologues was demonstrated.
Conclusion: In the elderly, heterologous CoVac/ChAd vaccination could induce NAb response against the WT and non-Omicron variants not different from the homologous ChAd/ChAd vaccination. Both regimens could not give adequate NAb of the Omicron strain. The heterologous vaccination, however, induced higher spike-specific Th1 cell response.
Key words: COVID-19 vaccine, Heterologous vaccination, Homologous vaccination, Elderly, Immune response