TY - JOUR
T1 - Therapeutic Vaccination With Recombinant Adenovirus Reduces Splenic Parasite Burden in Experimental Visceral Leishmaniasis
AU - Maroof, Asher
AU - Brown, Najmeeyah
AU - Smith, Barbara
AU - Hodgkinson, Michael R.
AU - Maxwell, Alice
AU - Losch, Florian O.
AU - Fritz, Ulrike
AU - Walden, Peter
AU - Lacey, Charles N. J.
AU - Smith, Deborah F.
AU - Aebischer, Toni
AU - Kaye, Paul M.
PY - 2012/3/1
Y1 - 2012/3/1
N2 - 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 IFN gamma(+)CD8(+) T cell responses, particularly to HASPB, became apparent. A single vaccination with Ad5-KH inhibited splenic parasite growth by similar to 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.
AB - 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 IFN gamma(+)CD8(+) T cell responses, particularly to HASPB, became apparent. A single vaccination with Ad5-KH inhibited splenic parasite growth by similar to 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.
UR - http://www.scopus.com/inward/record.url?scp=84863160177&partnerID=8YFLogxK
U2 - 10.1093/infdis/jir842
DO - 10.1093/infdis/jir842
M3 - Article
C2 - 22301630
VL - 205
SP - 853
EP - 863
JO - The Journal of Infectious Diseases
JF - The Journal of Infectious Diseases
IS - 5
ER -