Cellular Immune Responses to Nine Mycobacterium tuberculosis Vaccine Candidates following Intranasal Vaccination

Abstract

BackgroundThe identification of Mycobacterium tuberculosis vaccines that elicit a protective immune response in the lungs is important for the development of an effective vaccine against tuberculosis.Methods and Principal FindingsIn this study, a comparison of intranasal (i.n.) and subcutaneous (s.c.) vaccination with the BCG vaccine demonstrated that a single moderate dose delivered intranasally induced a stronger and sustained M. tuberculosis-specific T-cell response in lung parenchyma and cervical lymph nodes of BALB/c mice than vaccine delivered subcutaneously. Both BCG and a multicomponent subunit vaccine composed of nine M. tuberculosis recombinant proteins induced strong antigen-specific T-cell responses in various local and peripheral immune compartments. Among the nine recombinant proteins evaluated, the alanine proline rich antigen (Apa, Rv1860) was highly antigenic following i.n. BCG and immunogenic after vaccination with a combination of the nine recombinant antigens. The Apa-induced responses included induction of both type 1 and type 2 cytokines in the lungs as evaluated by ELISPOT and a multiplexed microsphere-based cytokine immunoassay. Of importance, i.n. subunit vaccination with Apa imparted significant protection in the lungs and spleen of mice against M. tuberculosis challenge. Despite observed differences in the frequencies and location of specific cytokine secreting T cells both BCG vaccination routes afforded comparable levels of protection in our study.Conclusion and SignificanceOverall, our findings support consideration and further evaluation of an intranasally targeted Apa-based vaccine to prevent tuberculosis.

A Single Dose of a DNA Vaccine Encoding Apa Coencapsulated with 6,6′-Trehalose Dimycolate in Microspheres Confers Long-Term Protection against Tuberculosis in Mycobacterium bovis BCG-Primed Mice

“…Subsequently, immunization with 3 doses of apa was shown to be highly immunogenic in a murine model (36). Recently, among the nine M. tuberculosis recombinant proteins evaluated, the Apa antigen was found to be highly antigenic following BCG vaccination (37). Our data on heterologous prime-boost immunization also confirmed this immunogenicity induced by Apa, after an intratracheal M. tuberculosis infection, and showed that this immunization lasts longer than the one conferred by BCG vaccination alone.…”

O-mannosylation of the Mycobacterium tuberculosis Adhesin Apa Is Crucial for T Cell Antigenicity during Infection but Is Expendable for Protection

“…Nonetheless, the ability of rApa to impart protection in this study is consistent with previous observation that i.n. subunit vaccination using rApa protein imparts notable protection in mice [18].…”

“…These mannose residues are absent in the recombinant form of Apa (rApa) expressed in E. coli , and the rApa is poorly recognized by T cells of BCG inoculated guinea pigs [14], [15]. We and others have identified Apa as a possible vaccine candidate against TB [16]–[18], but the role of glycosylation in inducing protective T cell immunity had not been studied.…”

Role of Diabetes in prevalence of Tuberculosis

“…The body's immune system, possess the capacity, to stop the bacteria to reproduce continually. Thus, the immune system can make the lung infection inactive (dormant state) [7]. On the other hand, if the body's immune system is not strong enough and cannot contain the TB bacteria, then the bacteria will reproduce (become active or reactivate) in the lungs and spread elsewhere in the body.…”