A novel multiepitope peptide vaccine with intrinsic adjuvant confers protective immunity in mice against tuberculosis

Tuberculosis remains a global health challenge with the only licensed vaccine, Bacillus Calmette-Guérin (BCG). Latent tuberculosis serves as a reservoir for TB infection. Over the past few years, protein subunit vaccines have gained research attention due to their safety and versatility. This study aimed to assess the protective efficacy of an immunoinformatically designed, expressed, and purified synthetic peptide vaccine candidate, VC28, incorporating epitopes from late-stage DosR proteins. The immunogenicity and protective efficacy of the VC28 vaccine were assessed in BALB/c mice.

The mice were immunized with VC28 alone or along with BCG. Effector, memory or regulatory T cell markers and APC activation markers, along with Th1-type cytokines, were studied in immunized mouse splenocytes. Lung bacterial load and pathology were studied after H37Rv challenge of immunized mice.

Increased frequency of effector and central memory T cells, along with increased antigen-specific IFN-γ producing CD4⁺ and CD8⁺ T cells, were seen in VC28 or BCG + VC28 immunized mice. Activated macrophages and dendritic cells further caused an augmented adaptive response and release of Th1 (IL-2, IFN-γ, TNF-α, CD40L) and Th17 (IL-17A) cytokines in immunized mice splenocyte culture supernatants. A reduction in bacterial load and reduced lung pathology were also observed in VC28 and BCG + VC28 immunized mice challenged with H37Rv Mtb strain.

VC28 and BCG + VC28 induced a robust antigen-specific immune response and enhanced macrophage and DC activation, suppressed Mtb infection and alleviated lung damage compared to unimmunised and BCG groups. These findings highlight the potential of VC28 as a vaccine candidate and adjuvant.