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A lipidated bi-epitope vaccine comprising of MHC-I and MHC-II binder peptides elicits protective CD4 T cell and CD8 T cell immunity against Mycobacterium tuberculosis.
Rai, Pradeep K; Chodisetti, Sathi Babu; Maurya, Sudeep K; Nadeem, Sajid; Zeng, Weiguang; Janmeja, Ashok K; Jackson, David C; Agrewala, Javed N.
Afiliación
  • Rai PK; CSIR-Institute of Microbial Technology, Chandigarh, India.
  • Chodisetti SB; CSIR-Institute of Microbial Technology, Chandigarh, India.
  • Maurya SK; Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA.
  • Nadeem S; CSIR-Institute of Microbial Technology, Chandigarh, India.
  • Zeng W; CSIR-Institute of Microbial Technology, Chandigarh, India.
  • Janmeja AK; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, 3010, Australia.
  • Jackson DC; Department of Pulmonary Medicine, Government Medical College and Hospital, Chandigarh, India.
  • Agrewala JN; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, 3010, Australia.
J Transl Med ; 16(1): 279, 2018 10 11.
Article en En | MEDLINE | ID: mdl-30305097
BACKGROUND: The clinical trials conducted at Chingleput India suggest that BCG fails to protect against tuberculosis (TB) in TB-endemic population. Recent studies advocate that non-tuberculous mycobacteria and latent Mycobacterium tuberculosis (Mtb) infection interferes in the antigen processing and presentation of BCG in inducing protective immunity against Mtb. Thereby, indicating that any vaccine that require extensive antigen processing may not be efficacious in TB-endemic zones. Recently, we have demonstrated that the vaccine candidate L91, which is composed of lipidated promiscuous MHC-II binder epitope, derived from latency associated Acr1 antigen of Mtb is immunogenic in the murine and Guinea pig models of TB and conferred better protection than BCG against Mtb. METHODS: In this study, we have used a multi-stage based bi-epitope vaccine, namely L4.8, comprising of MHC-I and MHC-II binding peptides of active (TB10.4) and latent (Acr1) stages of Mtb antigens, respectively. These peptides were conjugated to the TLR-2 agonist Pam2Cys. RESULTS: L4.8 significantly elicited both CD8 T cells and CD4 T cells immunity, as evidenced by increase in the enduring polyfunctional CD8 T cells and CD4 T cells. L4.8 efficiently declined Mtb-burden and protected animals better than BCG and L91, even at the late stage of Mtb infection. CONCLUSIONS: The BCG-L4.8 prime boost strategy imparts a better protection against TB than the BCG alone. This study emphatically denotes that L4.8 can be a promising future vaccine candidate for controlling active and latent TB.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacuna BCG / Antígenos de Histocompatibilidad Clase I / Linfocitos T CD4-Positivos / Antígenos de Histocompatibilidad Clase II / Linfocitos T CD8-positivos / Lípidos / Mycobacterium tuberculosis / Epítopos Límite: Animals Idioma: En Revista: J Transl Med Año: 2018 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacuna BCG / Antígenos de Histocompatibilidad Clase I / Linfocitos T CD4-Positivos / Antígenos de Histocompatibilidad Clase II / Linfocitos T CD8-positivos / Lípidos / Mycobacterium tuberculosis / Epítopos Límite: Animals Idioma: En Revista: J Transl Med Año: 2018 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido