Heterologous prime-boost vaccination with a non-replicative vaccinia recombinant vector expressing LACK confers protection against canine visceral leishmaniasis with a predominant Th1-specific immune response

Abstract

Leishmaniasis caused by Leishmania infantum is a severe endemic disease in the Mediterranean basin, being domestic dogs the main reservoir of the disease that plays a key role in the transmission to humans. Studies on vaccines against canine leishmaniasis, aimed to modify the T cell repertoire, have advanced in recent years. LACK vaccination assays, using protein or DNA vectors, show protection against cutaneous L. major infections by redirecting the early IL-4 responses to a protective Th1 response. The aim of this study was to define the effectiveness and type of immune response in a canine visceral leishmaniasis model of two poxvirus vectors (Western reserve strain, WR and modified vaccinia virus Ankara, MVA) expressing the LACK protein of L. infantum in prime/boost vaccination protocols. The results obtained showed that dog vaccination priming with DNA-LACK followed by a booster with MVA-LACK or rVV-LACK triggered a Th1 type of immune response, leading to protection against canine visceral leishmaniasis. This protection correlated with absence of visceral leishmaniasis symptoms, lower Leishmania-specific antibodies, higher degree of T cell activation in Leishmania-target organs and higher synthesis of Th1 cytokines. In addition, we found that dogs boosted with the non-replicative virus show less VL symptoms and higher degree of T cell activation, providing evidences for a clear advantage of MVA-LACK as a vaccination vector against canine visceral leishmaniasis.

Vaccine candidates for leishmaniasis: A review

“…A heterologous prime-boost regimen was also employed to immunize dogs against visceral leishmaniasis and elicited protection in 60% of immunized dogs [272]. Similarly, vaccination of dogs primed with LACK DNA followed by a booster of MVA or VV triggered Th1 immune response that leads to protection [303]. Recently, it has been shown that priming with TRYP followed by MVA booster was safe in dogs and immunogenically better than LACK/MVA vaccination [304].…”

Humoral and In Vivo Cellular Immunity against the Raw Insect-Derived Recombinant Leishmania infantum Antigens KMPII, TRYP, LACK, and papLe22 in Dogs from an Endemic Area

“…53,54 However, vaccine strategies, such as DNA or prime-boost vaccinations, which are able to induce a strong T h 1 immune response against these antigens, have proven able to obtain protection against L. infantum , probably by promoting a redirection of their T h 2 immune response to a T h 1 profile. 30,55 The lack of a standardized antigen is the main drawback of the LST. Leishmanin reagent is an amalgam of antigens, some of which could be activating a strong T h 1 immune response, such as TRYP, and others that could be inducing a T h 2 or weak T h 1 immune response, such as KMPII, LACK, or papLe22.…”

Making an anti-amastigote vaccine for visceral leishmaniasis: rational, update and perspectives

“…Induction of IL-12 is critical for vaccine efficiency [49] and many of these adjuvants activate the innate immune response via the Toll-like receptors (TLR), modeling the acquired immune responses [50,51]. Heterologous prime-boost immunization protocols involving recombinant virus, DNA or recombinant protein, have been also tested with various antigens to increase vaccine potency [52][53][54][55]. Recently, however, long lasting protective immunity has been associated to induction of antigen specific poly-functional T-cells, which express simultaneously IFNg, TNF-a and IL-2 [47].…”