Gene-based neonatal immune priming potentiates a mucosal adenoviral vaccine encoding mycobacterial Ag85B.

摘要: Tuberculosis remains a major public health hazard worldwide, with neonates and young infants potentially more susceptible to infection than adults. BCG, the only vaccine currently available, provides some protection against tuberculous meningitis in children but variable efficacy adults, is not safe use immune compromised individuals. A effective that could be given early life, also potentiate subsequent booster immunization, would represent significant advance. To test this proposition, we have generated gene-based vectors expressing Ag85B from Mycobacterium tuberculosis (Mtb) designed experiments their immunogenicity protective particularly when heterologous prime-boost combination, initial DNA component soon after birth. Intradermal delivery of vaccines elicited Th1-based responses neonatal mice did protect them aerosol challenge virulent Mtb H37Rv. Recombinant adenovirus encoding Ag85B, via intranasal route at six weeks age, moderate were poorly protective. However, priming following by mucosal boosting recombinant strong responses, as evidenced Ag85B-specific CD4+ CD8+ T cell both lung-associated lymph nodes spleen, quality these responding cells (assessed capacity secrete multiple antimicrobial factors), improved protection, indicated reduced bacterial burden lungs pulmonary TB challenge. These results suggest immunization may create favorable immunological environment potentiates effects vector same antigen. Our data indicate life mycobacterial antigens an appropriate setting can prime for immunity Mtb.