Peptides-Based Vaccine MP3RT Induced Protective Immunity Against Mycobacterium Tuberculosis Infection in a Humanized Mouse Model

Abstract

BackgroundTuberculosis (TB) is still a global infectious disease that seriously threatens human beings. The only licensed TB vaccine Bacille Calmette-Guérin (BCG)’s protective efficacy varies significantly among populations and regions. It is very urgent to develop more effective vaccines.MethodsIn this study, eleven candidate proteins of Mycobacterium tuberculosis were selected to predict peptides with high-affinity binding capacity for the HLA-DRB1*01:01 molecule. The immunodominant peptides were identified with the enzyme-linked immunospot assay (ELISPOT) and linked in silico to result in a novel polypeptide vaccine in Escherichia coli cells. The vaccine’s protective efficacy was evaluated in humanized and wild-type C57BL/6 mice. The potential immune protective mechanisms were explored with Enzyme-linked Immunosorbent Assay (ELISA), flow cytometry, and ELISPOT.ResultsSix immunodominant peptides screened from 50 predicted peptides were used to construct a new polypeptide vaccine named MP3RT. After challenge with M. tuberculosis, the colony-forming units (CFUs), lung lesion area, and the number of inflammatory cells in humanized mice rather than wild-type mice vaccinated with MP3RT were significantly lower than these in mice immunized with PBS. The humanized mice vaccinated with MP3RT revealed significant increases in IFN-γ cytokine production, IFN-γ+ T lymphocytes, CD3+IFN-γ+ T lymphocytes, and the MP3RT-specific IgG antibody.ConclusionsTaken together, MP3RT is a promising peptides-based TB vaccine characterized by inducing high levels of IFN-γ and CD3+IFN-γ+ T lymphocytes in humanized mice. These new findings will lay a foundation for the development of peptides-based vaccines against TB.

Differential Diagnosis of Latent Tuberculosis Infection and Active Tuberculosis: A Key to a Successful Tuberculosis Control Strategy

“…Our previous research and other large amounts of data show that TB is not only an infectious disease but also an immune disease (Gong et al, 2018(Gong et al, , 2021Li et al, 2020;Liang et al, 2021;Rambaran et al, 2021). The pathogenesis of TB is closely related to the host's immune response.…”

“…Previous studies revealed that neutrophils contribute to immune resistance to TB by producing antimicrobial peptides, facilitating the migration of DCs, and exerting protective effects on the oxidative killing of mycobacteria in TB granulomas (Martineau et al, 2007;Yang et al, 2012). Furthermore, accumulating evidence shows that B cells, natural killer (NK) cells, and mucosal-associated invariant T (MAIT) cells also play an important role in the immune response against M. tuberculosis by interacting with various immune cells, such as macrophages, T cells, and neutrophils (Achkar et al, 2015;Allen et al, 2015;Gong et al, 2021;Sakai et al, 2021).…”

“…The limitation of these studies is that they only focused on epitopes singly identified from CD4 + T lymphocytes [helper T lymphocytes (Th)] or CD8 + T lymphocytes (CTLs) rather than epitopes synchronously identified from Th cells, CTL cells, and B cells. Although the traditional view is that the host clearance and killing of M. tuberculosis mainly depend on CD4 + T lymphocytes and CD8 + T lymphocytes, accumulated data show that B lymphocytes also play an irreplaceable role in fighting against M. tuberculosis (Gong et al, 2018(Gong et al, , 2021Watson et al, 2021). Therefore, peptides binding to Th cells, CTL cells, and B cells should be considered when designing new candidate biomarkers based on epitopes for distinguishing LTBI from aTB and BCG-vaccinated HCs.…”

“…Furthermore, MHC molecules affect the efficacy of peptidebased vaccines and diagnosis (Gong et al, 2021;Jia et al, 2021). It is well known that recognition peptides produced by CD4 + or CD8 + T cells are mostly restricted to MHC-II or MHC-I molecules, respectively.…”

COVID-19 pandemic: SARS-CoV-2 specific vaccines and challenges, protection via BCG trained immunity, and clinical trials

“…As an old vaccine, BCG has been widely used to fight against TB for decades [ 51 ]. Interestingly, a growing number of studies have demonstrated that BCG vaccine induced a significantly higher levels of IFN-γ and IL-10, giving it the prophylactic effect against bacterial and viral infections in humans, such as experimental yellow fever, human papillomavirus (HPV), respiratory syncytial virus (RSV), influenza A virus (H1N1), herpes simplex virus (HSV), hepatitis B virus (HBV), melanoma, bladder cancer, severe oral aphthosis, S. pneumoniae or virus infection, and Salmonella typhi [ 37 , 52 ].…”