Protective immune response against cutaneous leishmaniasis by prime/booster immunization regimens with vaccinia virus recombinants expressing Leishmania infantum p36/LACK and IL-12 in combination with purified p36

• Published in: Microbes and infection 2001-07, Vol.3 (9), p.701-711
• Main Authors: Gonzalo, Rosa María, Rodríguez, Juan Ramón, Rodríguez, Dolores, González-Aseguinolaza, Gloria, Larraga, Vicente, Esteban, Mariano
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Protozoan - blood; Antigens, Protozoan; Biological and medical sciences; Crystallins - genetics; Crystallins - immunology; Crystallins - metabolism; cytokines; Cytokines - biosynthesis; Female; Fundamental and applied biological sciences. Psychology; g-Interferon; Immunization Schedule; Immunization, Secondary; Interleukin-12 - genetics; Interleukin-12 - immunology; Interleukin-12 - metabolism; LACK protein; Leishmania infantum; Leishmania infantum - immunology; leishmaniasis; Leishmaniasis, Cutaneous - immunology; Leishmaniasis, Cutaneous - prevention & control; Mice; Mice, Inbred BALB C; NAD(P)H Dehydrogenase (Quinone) - genetics; NAD(P)H Dehydrogenase (Quinone) - immunology; NAD(P)H Dehydrogenase (Quinone) - metabolism; p36 protein; Protozoa; Protozoan Proteins - genetics; Protozoan Proteins - immunology; Protozoan Proteins - metabolism; Protozoan Vaccines - immunology; Recombinant Proteins - immunology; Recombinant Proteins - metabolism; rodent; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Synthetic - immunology; Vaccinia virus; Vaccinia virus - genetics; zeta-Crystallins
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/S1286-4579(01)01426-5

In susceptible mice Leishmania infection triggers a CD4 + Th2 response that has been correlated with evasion of the host immune system. To develop approaches that might trigger a Th1 response leading to protection against Leishmania we generated vaccinia virus recombinants (VVr) expressing the relevant p36/LACK protein of Leishmania infantum (VVp36) or co-expressing p36/LACK and interleukin-12 (VVp36IL12). Susceptible BALB/c mice were immunized with the VVr in various prime/booster protocols that included purified p36/LACK protein, followed 3 weeks later by a challenge with live L. major promastigotes. The course of the infection was monitored by measuring lesion development, parasite load and immunological parameters (IFN-γ and IL-10 secretion by in vitro-stimulated lymphocytes, and specific IgG isotypes), before and after challenge. We found protocols of prime/booster immunization (VVp36/VVp36; VVp36IL12/p36; p36/VVp36IL12) that elicited different levels of protection in infected animals. The protocol of priming with purified p36 followed by a booster with VVp36IL12 induced 52% reduction in lesion size and a two-log unit reduction in parasite load. This partial protection correlated with activation of a specific Th1 type of immune response. These protocols could be of interest in the prophylaxis against Leishmania spp. and other parasitic diseases.