Comparative study of humoral and cellular immunity against SARS-CoV-2 induced by different COVID-19 vaccine types: Insights into protection against wildtype, Delta and JN.1 omicron strains.

We investigated the effectiveness of different COVID-19 vaccinations administered in Pakistan by studying the effect of inactivated virus, mRNA and vector formulations. This study in 916 participants was conducted between October 2021 and July 2022. Subjects receiving inactivated (A), mRNA (B), one-dose vector (C), and two-dose vector (D) vaccines were sampled at baseline, 6, 12, and 24 weeks. Serum IgG antibodies to wildtype Spike and its receptor binding domain (RBD) were measured. Pseudovirus particle-based neutralizing assays against wildtype, Delta, and JN.1 variants were performed. T cell IFN-γ responses to SARS-CoV-2 antigens were measured. Participants were aged 37.05 ± 14.44 years and comprised 48.6 % females. Baseline Spike seropositivity rose from 90 % to 96 % by 24 weeks; and 40 % to 90 % against RBD. Group B participants had the highest anti-RBD levels which peaked by 6 weeks. IgG RBD in group A and C increased up until 24 weeks. Anti-RBD levels were reduced in those over 50 years. At baseline neutralizing titers were present at 38.5 % against wildtype and in 34.2 % against Delta variants. Titers doubled in vaccine groups A-C by 12 weeks, with highest titers in B and lowest in group C participants. At baseline, neutralizing titers against the JN.1 variant were absent but low titers were evident in 10 % of participants after 12 weeks. T cell reactivity to SARS-CoV-2 increased from 31 % at baseline to 50 % in group A and 73 % in group B participants by 6 weeks after vaccination. Presence of immunity against wildtype and Delta variants in one-third of participants at baseline could be due to sub-clinical infections. Increase in humoral and cellular immunity was greater after mRNA as compared with inactivated vaccinations. As COVID-19 morbidity in the population remained low, our data supports effectiveness of multiple vaccine formulations in protecting against severe COVID-19 in this high transmission population.