Therapeutic Vaccination With Recombinant Adenovirus Reduces Splenic Parasite Burden in Experimental Visceral Leishmaniasis
Open Access
- 1 February 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in The Journal of Infectious Diseases
- Vol. 205 (5), 853-863
- https://doi.org/10.1093/infdis/jir842
Abstract
Therapeutic vaccines, when used alone or in combination therapy with antileishmanial drugs, may have an important place in the control of a variety of forms of human leishmaniasis. Here, we describe the development of an adenovirus-based vaccine (Ad5-KH) comprising a synthetic haspb gene linked to a kmp11 gene via a viral 2A sequence. In nonvaccinated Leishmania donovani–infected BALB/c mice, HASPB- and KMP11-specific CD8+ T cell responses were undetectable, although IgG1 and IgG2a antibodies were evident. After therapeutic vaccination, antibody responses were boosted, and IFNγ+CD8+ T cell responses, particularly to HASPB, became apparent. A single vaccination with Ad5-KH inhibited splenic parasite growth by ∼66%, a level of efficacy comparable to that observed in early stage testing of clinically approved antileishmanial drugs in this model. These studies indicate the usefulness of adenoviral vectors to deliver leishmanial antigens in a potent and host protective manner to animals with existing L. donovani infection.Keywords
This publication has 49 references indexed in Scilit:
- Single Dose Novel Salmonella Vaccine Enhances Resistance against Visceralizing L. major and L. donovani Infection in Susceptible BALB/c MicePLoS Neglected Tropical Diseases, 2011
- Vaccines for the Leishmaniases: Proposals for a Research AgendaPLoS Neglected Tropical Diseases, 2011
- A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adultsVaccine, 2010
- Loss of Dendritic Cell Migration and Impaired Resistance toLeishmania donovaniInfection in Mice Deficient in CCL19 and CCL21The Journal of Immunology, 2006
- E unum pluribus: multiple proteins from a self-processing polyproteinTrends in Biotechnology, 2006
- Adoptive Immunotherapy against Experimental Visceral Leishmaniasis with CD8+T Cells Requires the Presence of Cognate AntigenInfection and Immunity, 2006
- Differential Immunogenicity of Various Heterologous Prime-Boost Vaccine Regimens Using DNA and Viral Vectors in Healthy VolunteersPublished by The American Association of Immunologists ,2005
- Expression of hydrophilic surface proteins in infective stages of Leishmania donovaniMolecular and Biochemical Parasitology, 1999
- Serodiagnosis of Leishmania donovani infections: assessment of enzyme-linked immunosorbent assays using recombinant L. donovani gene B protein (GBP) and a peptide sequence of L. donovani GBPTransactions of the Royal Society of Tropical Medicine and Hygiene, 1999
- Comparison of the efficacies of various formulations of amphotericin B against murine visceral leishmaniasisAntimicrobial Agents and Chemotherapy, 1997