Full text
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| Author(s): |
Rafael Ribeiro Almeida
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2011-06-10 |
| Examining board members: |
Edecio Cunha Neto;
Silvia Beatriz Boscardin;
Luis Carlos de Souza Ferreira
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| Advisor: | Edecio Cunha Neto |
| Abstract | |
The AIDS pandemic is a worldwide major public health problem and requires the development of an effective vaccine. An ideal vaccine approach based on cellular immune responses against HIV-1 should induce an immune response mediated by both CD4+ and CD8+ T cells. HIV-1 genetic diversity is a major concern for developing a vaccine and consensus sequences have been used to circumvent the barrier posed by this diversity. The appropriate choice of antigens to compose the vaccines is also relevant, since proteins such as Gag and Vif have been shown to be immunogenic, while some studies have shown that Env has immunosuppressive characteristics and cellular responses against this antigen can be harmful to vaccinated individuals. Our group has demonstrated that a DNA vaccine (HIVBr18) encoding promiscuous multiple HLA-DR binding, conserved B-subtype HIV-1 CD4+ T cell epitopes was able to induce a broad, polyfunctional and long lasting T cell response in BALB/c and HLA transgenic mice. In this work we identified 34 promiscuous and conserved sequences within the group M HIV-1 consensus of the consensus sequence, potentially recognized by CD4+ T cells. A DNA vaccine (HIVBr27) encoding 27 of the 34 peptides (except the 7 Env identified peptides) induced a broader and higher magnitude T cell response than HIVBr18 vaccine in BALB/c mice. Moreover, the vaccine HIVBr27 induced a higher frequency of polyfunctional CD4+ and CD8+ T cells, able to proliferate and produce the cytokines IFN-gama and TNF-alfa. We also developed a DNA vaccine (HIVenv7) encoding the 7 HIV-1 Env identified peptides. Co-immunization with HIVenv7+HIVBr27 reduced the breadth of the cellular immune response against the HIVBr27 encoded peptides. Besides, co-imunization reduced the magnitude of the response and the frequency of polyfunctional CD4+ and CD8+ T cells against the pool of 27 peptides encoded by this vaccine. The HIVBr27 vaccine, designed to induce a broad and intense CD4+ T cell response against promiscuous and conserved peptides within the group M HIV-1 consensus of the consensus sequence, is more immunogenic and more complete than the vaccine HIVBr18, having the potential to provide, with wide population coverage, immunity against various circulating subtypes of the virus. The phenomenon observed in the co-immunization with HIVenv7 suggests that the inclusion of the envelope in immunogens against HIV-1 may be harmful. On the other hand, these results suggest that HIVenv7 is a promising target for immune therapies aimed at inducing immunosuppression (AU) | |
| FAPESP's process: | 09/03141-9 - Immunogenicity of a DNA vaccine containing M type HIV-1 epitopes in BALB/c mice |
| Grantee: | Rafael Ribeiro Almeida |
| Support Opportunities: | Scholarships in Brazil - Master |