A multistage Sendai virus vaccine incorporating latency-associated antigens induces protection against acute and latent tuberculosis.
Emerg Microbes Infect
; 13(1): 2300463, 2024 Dec.
Article
in En
| MEDLINE
| ID: mdl-38164736
ABSTRACT
One-quarter of the world's population is infected with Mycobacterium tuberculosis (Mtb). After initial exposure, more immune-competent persons develop asymptomatic latent tuberculosis infection (LTBI) but not active diseases, creates an extensive reservoir at risk of developing active tuberculosis. Previously, we constructed a novel recombinant Sendai virus (SeV)-vectored vaccine encoding two dominant antigens of Mtb, which elicited immune protection against acute Mtb infection. In this study, nine Mtb latency-associated antigens were screened as potential supplementary vaccine candidate antigens, and three antigens (Rv2029c, Rv2028c, and Rv3126c) were selected based on their immune-therapeutic effect in mice, and their elevated immune responses in LTBI human populations. Then, a recombinant SeV-vectored vaccine, termed SeV986A, that expresses three latency-associated antigens and Ag85A was constructed. In murine models, the doses, titers, and inoculation sites of SeV986A were optimized, and its immunogenicity in BCG-primed and BCG-naive mice were determined. Enhanced immune protection against the Mtb challenge was shown in both acute-infection and latent-infection murine models. The expression levels of several T-cell exhaustion markers were significantly lower in the SeV986A-vaccinated group, suggesting that the expression of latency-associated antigens inhibited the T-cell exhaustion process in LTBI infection. Hence, the multistage quarter-antigenic SeV986A vaccine holds considerable promise as a novel post-exposure prophylaxis vaccine against tuberculosis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tuberculosis
/
Latent Tuberculosis
/
Mycobacterium tuberculosis
Type of study:
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Emerg Microbes Infect
Year:
2024
Document type:
Article