ABSTRACT
COVID-19 is caused by coronavirus SARS-CoV-2. Current systemic vaccines generally provide limited protection against viral replication and shedding within the airway. Recombinant VSV (rVSV) is an effective vector which inducing potent and comprehensive immunities. Currently, there are two clinical trials investigating COVID-19 vaccines based on VSV vectors. These vaccines were developed with spike protein of WA1 which administrated intramuscularly. Although intranasal route is ideal for activating mucosal immunity with VSV vector, safety is of concern. Thus, a highly attenuated rVSV with three amino acids mutations in matrix protein (VSVMT) was developed to construct safe mucosal vaccines against multiple SARS-CoV-2 variants of concern. It demonstrated that spike protein mutant lacking 21 amino acids in its cytoplasmic domain could rescue rVSV efficiently. VSVMT indicated improved safeness compared with wild-type VSV as the vector encoding SARS-CoV-2 spike protein. With a single-dosed intranasal inoculation of rVSVΔGMT-SΔ21, potent SARS-CoV-2 specific neutralization antibodies could be stimulated in animals, particularly in term of mucosal and cellular immunity. Strikingly, the chimeric VSV encoding SΔ21 of Delta-variant can induce more potent immune responses compared with those encoding SΔ21 of Omicron- or WA1-strain. VSVMT is a promising platform to develop a mucosal vaccine for countering COVID-19.
ABSTRACT
The intranasal route is one of the main routes of Mycobacterium leprae infection and there is paucity of information regarding the mode of spread of the pattern. The adherence of M. leprae to the nasal mucosa, its trapping within the sinuses of the head, and its fate after entry into the host was studied using mouse model. A comparison of the adherence profile of M. leprae and Mycobacterium tuberculosis showed that while larger numbers of M. tuberculosis were demonstrated within lungs, greater numbers of M. leprae were present within the sinuses of the head. Adherence of M. leprae to the nasal mucosa was dependent on surface integrity since opsonization and heat killing resulted in decreased numbers of M. leprae in the nasal sinuses and a greater amount entering the lungs. The adherence appeared to the independent of the viability of the bacilli, as similar numbers of formalin-fixed, rifampicin -treated and viable M. leprae entered the lungs in the initial stages. However the numbers of rifampicin-treated M. leprae in the nasal sinuses were 12-fold lower than the numbers of viable M. leprae. These results indicated that both viability and surface integrity were important in the entry of M. leprae and it's consequent dissemination.