RESUMO
In chronic HIV infection a progressive Th1 to Th2/Th0 cytokine-profile shift is related to disease progression. One of the possible benefits of a therapeutic vaccination might be to counterbalance this phenomenon to allow viral replication control under a Th1-type immune response. TERAVAC-HIV-1 is a multiantigenic formulation vaccine candidate against HIV-1 which comprises the recombinant protein CR3 that contains T cell epitopes and the surface and nucleocapsid antigens of Hepatitis B Virus (HBV). Previous studies showed that such virus like particles of the HBV provide a Th1 adjuvant effect. The present studies examined the capacity of TERAVAC to elicit a Th1 response in the presence of an ongoing HIV-specific Th2-type response in Balb/c mice. To examine this issue, we injected subcutaneously the animals with CR3 or viral lysate in alum which resulted in a Th2-type response. The CR3-specific Th2-type response was verified by induction of IL-4 and IL-10 secretion in ex vivo stimulated splenocytes without secretion of IFN-γ and IgG2a antibodies in serum. Further subcutaneous and simultaneous subcutaneous-nasal immunizations of the same mice with TERAVAC promoted IFN-γ secretion and production of IgG2a antibodies in accordance with a Th1-type response. This result suggests a therapeutic benefit of this vaccine candidate in the restoration of the Th1-type HIV-specific cellular response in seropositive patients.
Assuntos
Vacinas contra a AIDS/farmacologia , Citocinas/imunologia , Anticorpos Anti-HIV/imunologia , HIV-1/imunologia , Imunoglobulina G/imunologia , Vacinas contra a AIDS/genética , Vacinas contra a AIDS/imunologia , Animais , Citocinas/sangue , Anticorpos Anti-HIV/sangue , HIV-1/genética , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Imunoglobulina G/sangue , Camundongos , Camundongos Endogâmicos BALB C , Proteínas do Nucleocapsídeo/genética , Proteínas do Nucleocapsídeo/imunologia , Proteínas do Nucleocapsídeo/farmacologia , Células Th1 , Células Th2 , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/farmacologiaRESUMO
Amebiasis and rabies are public health problems, and they have in common a poor inflammatory effect in the target organs that they affect. In the GenBank, it was found that the anti-inflammatory peptide monocyte locomotion inhibitory factor (MLIF) produced by Entamoeba histolytica homologates 80%, with a fragment of the N protein of the rabies virus. We speculated if the N protein could contribute to the scant inflammatory reaction produced by rabies virus in central nervous system. The N protein was obtained and studied in vitro and in vivo. The N protein, as MLIF, inhibited the respiratory burst in human mononuclear phagocytes (43%, p<0.05), but in contrast to MLIF, it increased chemotaxis and it did not significantly inhibit delayed hypersensitivity skin reaction to 1-chloro-2-4-dinitrobenzene in guinea pigs. Therefore, the full peptide sequence has to be present or it has to be cleaved-free from the large recombinant N protein molecule (55 kDa) to become active.