Immunogenicity of COVID-19 Vaccines in the Upper Respiratory Tract: A Comparative Study of Pfizer-BioNTech and Johnson & Johnson Vaccines among Ugandan adults

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 immune responses among Pfizer-BioNTech and Johnson & Johnson (J&J) COVID-19 vaccine recipients in Uganda. 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 (T _RM ) 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 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) T cells among J&J recipients compared to Pfizer-BioNTech. Furthermore, J&J recipients showed a significantly higher abundance of CD4 + CD69+ T _RM cells (p = 0.0182) compared to Pfizer. Conversely, proportions of SARS-CoV-2 specific nasal CD8 + T cells expressing IFN-γ, Perforin and TNF were higher among Pfizer recipients four weeks after the first dose. On the other hand, J&J recipients revealed significantly higher CD8 + IFN-γ+ (p = 0.05) and CD107a+ (p = 0.05) responses at week 12 compared to Pfizer group. Taken together, our findings demonstrate the induction of nasal T-cell responses to COVID-19 vaccination in Ugandan volunteers, with notable differences observed between the J&J and Pfizer-BioNTech vaccine platforms. These data highlight the need to better understand mucosal immunity to COVID-19 and other vaccines, especially in low- and middle-income settings.