Analysis of Immunogenicity and protection generated by third generation immunogens pVAX1-FSD and pVAX1-SP against experimental cutaneous leishmaniasis

Author(s)

Bruno Luiz Soares Campos

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
• Defense date: 2015-04-17

Examining board members

Luiz Felipe Domingues Passero; André Gustavo Tempone Cardoso; Norival Kesper Junior

• Advisor: Luiz Felipe Domingues Passero

Abstract

American tegumentar leishmaniasis is an infectious disease, widespread, and in Brazil the species L. (V.) braziliensis and L. (L.) amazonensis are the most relevant in medical-epidemiological studies. Due to the epidemiological impact of leishmaniasis, prophylactic measures should be developed to control this disease, such as vaccines. Therefore, the present study aimed to evaluate the immunogenicity and the protective potential of two vaccine candidates known as iron superoxide dismutase (FSD) and serine peptidase (SP). FSD- and SP-coding genes were synthesized and cloned into plasmid pVAX1 (pVAX1-FSD and pVAX1-SP). BALB/c mice were immunized with both candidates at a concentration of 1.0 ug/uL, three times at intervals of 15 days and challenged or not with L. (L.) amazonensis promastigotes. Animals were evaluated clinically, immunologically and parasitologically in the studies of immunogenicity and protection. The results showed that both vaccines presented low immunogenicity, and after immunization BALB/c mice did not show significant changes in CD4 T lymphocytes, by the other side, the frequency of IFN-y and TNF-alfa producing cells were low. However, after challenge pVAX1-FSD-immunized mice presented a mixed Th1 and Th2 immune response, due to the high frequencies of IFN-ye IL-4-producing T lymphocytes, with association to high levels of IgG1 and IgG2a isotypes, leading to parasite burden decreasing. pVAX1-SP vaccine candidate also induced mixed immune response in animals, however high frequencies of IL-10-producing CD8 T lymphocytes was found, justifying the absence of protection in these animals (AU)

• FAPESP's process: 12/05219-8 - Analysis of immunogenicity and protection generated by third-generation vaccines pVAX1-FSD and pVAX1-SP against experimental American Tegumentar Leishmanasis
• Grantee: Bruno Luiz Soares Campos
• Support Opportunities: Scholarships in Brazil - Master