Booster with intranasal vaccine candidate Mambisa activates the expression of tissue resident memory T cell markers

The study evaluates the efficacy of the nasal booster vaccine candidate Mambisa in the activation of tissue-resident memory T cells (TRM), that are essential in mucosal immunity against respiratory infections such as COVID-19.Mambisa, developed by the Center for Genetic Engineering and Biotechnology (CIGB) in Cuba, combines the RBD protein of SARS-CoV-2 and the HBcAg protein of hepatitis B, and is administered nasally.The preclinical study in mice showed that the nasal administration of Mambisa significantly increased the expression of CD69, and CD103 (TRM markers) in the lungs, while increased FOXP3 expression was also observed.Foxp3 is essential for the development and function of Treg cells, and can influence the activation and regulation of TRM cells.These results suggest that the combination of RBD and HBcAg induces an effective local immune response, with a synergistic effect that enhances TRM cell activation in tissues.Furthermore, mice immunized with Mambisa showed higher RBD-specific IgG antibody titers and increased neutralizing activity against the virus, compared to formulations with only RBD or HBcAg.In a study with nasal samples from 48 COVID-19 convalescent individuals receiving a booster shot with either Mambisa or intramuscular vaccine Abdala significant increases in the expression of genes associated with TRM (CD69, CD103) and effector immune responses (INFG, GZMB, CXCL10) were detected in the Mambisa group, indicating a local activation in the intranasal mucosa.In contrast, there were no significant differences in these markers in the Abdala group.TRM cells, residing in tissues such as the respiratory tract, act as a first line of defense, blocking viral replication and reducing transmission.The Mambisa formulation, by activating these markers, could enhance mucosal immunity, which is crucial in preventing emerging infections and variants.Moreover, the use of HBcAg as an adjuvant improves the RBD antigen presentation, enhancing specific T-cell and antibody responses.In summary, these results suggest that Mambisa is a promising candidate for inducing durable local immunity against SARS-CoV-2, with the potential to reduce transmission and mitigate future outbreaks.