Immunogenicity of COVID-19 vaccines in the upper respiratory tract: a comparative study of Pfizer-BioNTech and Johnson & Johnson vaccines among Ugandan adults

Abstract Background COVID-19 vaccination has been shown to elicit robust systemic immune responses against SARS-CoV-2. However, little is known about vaccine-induced mucosal responses in the upper respiratory tract (URT), particularly in sub-Saharan Africa. Here, we characterized nasal and peripheral blood immune responses among Pfizer-BioNTech and Johnson & Johnson (J&J) COVID-19 vaccine recipients in Uganda. Methods This was an observational prospective cohort sub-study evaluating URT and systemic T cell responses in 21 Ugandan adults receiving either a single dose of J&J Ad26.COV2. S ( n = 7) at enrolment or two doses of Pfizer-BioNTech BNT162b2 ( n = 14) at enrolment and week 4 Study visits. T-cell responses were characterized by flow cytometry using nasopharyngeal (NP) swabs and peripheral blood mononuclear cell (PBMC) samples collected at enrolment, weeks 4 and 12. Changes in immune responses over time and differences between vaccine groups were evaluated using linear mixed models and non-parametric Mann-Whitney test respectively. A p-value < 0.05 was considered statistically significant. Results Overall, we observed a significant increase in the proportions of CD8 + T cells in the nasal mucosa ( p = 0.0500) and peripheral blood ( p = 0.0484). Additionally, CD8 + tissue-resident memory (TRM) T cells identified by co-expression of CD69 and CD103, showed an increased abundance in the upper respiratory tract ( p = 0.2469), accompanied by a simultaneous significant decrease in their proportions in blood ( p = 0.0300) following vaccination. Comparison of immune responses between the two vaccine groups at 4 weeks after the first vaccination dose for Pfizer and only dose for J&J revealed significantly higher immune cell counts of CD45+ ( p = 0.0182), CD3+ ( p = 0.0136), CD4+ ( p = 0.0091), and CD8+ ( p = 0.0182) among J&J recipients compared to Pfizer-BioNTech. CD4 + CD69+ TRM T cell abundance was also significantly higher in J&J recipients ( p = 0.0182). Conversely, Pfizer-BioNTech recipients showed higher proportions of SARS-CoV-2-specific nasal CD8 + T cells expressing IFN-γ, perforin, and TNF at week 4 while J&J recipients revealed increased proportions of CD8 + T cells expressing IFN-γ and CD107a (both p = 0.0500) compared to Pfizer-BioNTech recipients at week 12. Conclusion Our findings demonstrate that both J&J and Pfizer-BioNTech vaccines induced nasal and systemic T cell responses in Ugandan adults, with response patterns varying by vaccine platform and time point. While J&J vaccination was associated with higher early nasal immune cell abundance, Pfizer-BioNTech vaccination elicited distinct immune responses, with changes observed across study visits. These data highlight the need to better understand mucosal immunity to COVID-19 and other vaccines, especially in low- and middle-income settings.