BACKGROUND: Emergence of resistance against commonly available drugs poses a major threat in the treatment of visceral leishmaniasis (VL), particularly in the Indian subcontinent. Absence of any licensed vaccine against VL emphasizes the urgent need to develop an effective alternative vaccination strategy. METHODOLOGY: We developed a novel heterologous prime boost immunization strategy using kinetoplastid membrane protein-11 (KMP-11) DNA priming followed by boosting with recombinant vaccinia virus (rVV) expressing the same antigen. The efficacy of this vaccination regimen in a murine and hamster model of visceral leishmaniasis caused by both antimony resistant (Sb-R) and sensitive (Sb-S) Leishmania (L.) donovani is examined. RESULT: Heterologous prime-boost (KMP-11 DNA/rVV) vaccination was able to protect mice and hamsters from experimental VL induced by both Sb-S and Sb-R-L. (L.) donovani isolates. Parasite burden is kept significantly low in the vaccinated groups even after 60 days post-infection in hamsters, which are extremely susceptible to VL. Protection in mice is correlated with strong cellular and humoral immune responses. Generation of polyfunctional CD8(+) T cell was observed in vaccinated groups, which is one of the most important prerequisite for successful vaccination against VL. Protection was accompanied with generation of antigen specific CD4(+) and CD8(+) cells that produced effector cytokines such as IFN-γ, IL-2 and TNF-α. KMP-11-DNA/rVV vaccination also developed strong cytotoxic response and reversed T-cell impairment to induce antigen specific T cell proliferation. CONCLUSION: KMP-11 is a unique antigen with high epitope density. Heterologous prime boost vaccination activates CD4(+) and CD8(+) T-cell mediated immunity to confer resistance to VL. This immunization method also produces high quality T-cells secreting multiple effector cytokines thus enhancing durability of the immune response. Thus the vaccination regime as described in the present study could provide a potent strategy for future anti-leishmanial vaccine development.
BACKGROUND: Emergence of resistance against commonly available drugs poses a major threat in the treatment of visceral leishmaniasis (VL), particularly in the Indian subcontinent. Absence of any licensed vaccine against VL emphasizes the urgent need to develop an effective alternative vaccination strategy. METHODOLOGY: We developed a novel heterologous prime boost immunization strategy using kinetoplastid membrane protein-11 (KMP-11) DNA priming followed by boosting with recombinant vaccinia virus (rVV) expressing the same antigen. The efficacy of this vaccination regimen in a murine and hamster model of visceral leishmaniasis caused by both antimony resistant (Sb-R) and sensitive (Sb-S) Leishmania (L.) donovani is examined. RESULT: Heterologous prime-boost (KMP-11 DNA/rVV) vaccination was able to protect mice and hamsters from experimental VL induced by both Sb-S and Sb-R-L. (L.) donovani isolates. Parasite burden is kept significantly low in the vaccinated groups even after 60 days post-infection in hamsters, which are extremely susceptible to VL. Protection in mice is correlated with strong cellular and humoral immune responses. Generation of polyfunctional CD8(+) T cell was observed in vaccinated groups, which is one of the most important prerequisite for successful vaccination against VL. Protection was accompanied with generation of antigen specific CD4(+) and CD8(+) cells that produced effector cytokines such as IFN-γ, IL-2 and TNF-α. KMP-11-DNA/rVV vaccination also developed strong cytotoxic response and reversed T-cell impairment to induce antigen specific T cell proliferation. CONCLUSION: KMP-11 is a unique antigen with high epitope density. Heterologous prime boost vaccination activates CD4(+) and CD8(+) T-cell mediated immunity to confer resistance to VL. This immunization method also produces high quality T-cells secreting multiple effector cytokines thus enhancing durability of the immune response. Thus the vaccination regime as described in the present study could provide a potent strategy for future anti-leishmanial vaccine development.
Authors: Gustavo Domínguez-Bernal; Pilar Horcajo; José A Orden; José A Ruiz-Santa-Quiteria; Ricardo De La Fuente; Lara Ordóñez-Gutiérrez; Abel Martínez-Rodrigo; Alicia Mas; Javier Carrión Journal: Parasit Vectors Date: 2015-12-09 Impact factor: 3.876
Authors: Agenor de Castro Moreira dos Santos Júnior; Dário Eluan Kalume; Ricardo Camargo; Diana Paola Gómez-Mendoza; José Raimundo Correa; Sébastien Charneau; Marcelo Valle de Sousa; Beatriz Dolabela de Lima; Carlos André Ornelas Ricart Journal: PLoS One Date: 2015-09-18 Impact factor: 3.240
Authors: Malcolm S Duthie; Michelle Favila; Kimberley A Hofmeyer; Yeung L Tutterrow; Steven J Reed; John D Laurance; Alessandro Picone; Jeffrey Guderian; H Remy Bailor; Aarthy C Vallur; Hong Liang; Raodoh Mohamath; Julie Vergara; Randall F Howard; Rhea N Coler; Steven G Reed Journal: Vaccine Date: 2016-05-01 Impact factor: 3.641