Pam3CSK4 adjuvant given intranasally boosts anti-Leishmania immunogenicity but not protective immune responses conferred by LaAg vaccine against visceral leishmaniasis.

The use of adjuvants in vaccine formulations is a well-established practice to improve immunogenicity and protective immunity against diseases. Previously, we have demonstrated the feasibility of intranasal vaccination with the antigen of killed Leishmania amazonensis promastigotes (LaAg) against experimental leishmaniasis. In this work, we sought to optimize the immunogenic effect and protective immunity against murine visceral leishmaniasis conferred by intranasal delivery of LaAg in combination with a synthetic TLR1/TLR2 agonist (Pam3CSK4). Intranasal vaccination with LaAg/PAM did not show toxicity or adverse effects, induced the increase of delayed-type hypersensitivity response and the production of inflammatory cytokines after parasite antigen recall. However, mice vaccinated with LaAg/PAM and challenged with Leishmania infantum presented significant reduction of parasite burden in both liver and spleen, similar to those vaccinated with LaAg. Although LaAg/PAM intranasal vaccination had induced higher frequencies of specific CD4+ and CD8+ T cells and increased levels of IgG2a antibody isotype in serum, both LaAg and LaAg/PAM groups presented similar levels of IL-4 and IFN-y and decreased production of IL-10 when compared to controls. Our results provide the first evidence of the feasibility of intranasal immunization with antigens of killed Leishmania in association with a TLR agonist, which may be explored for developing an effective and alternative strategy for vaccination against visceral leishmaniasis.

Human cytomegalovirus infection and abortion: an immunohistochemical study.

BACKGROUND: Cytomegalovirus (HCMV) has been described in abortion tissues, but seldom associated with inclusion bodies. However, the possible pathogenic role of this virus in abortion is under discussion. We attempted to verify the relationship between HCMV antigens in tissues from first trimester abortions presenting with inflammatory lesions. MATERIAL/METHODS: Sixteen cases of first trimester abortions with inflammatory lesions were selected from 340 cases studied at the Pathology Unit of the University Hospital in Vit ria, Esp rito Santo State, Brazil. Paraffin-embedded sections were subjected to indirect immunofluorescence (IFI) and immunoperoxidase (PAP), using monoclonal antibodies directed against immediate early (IEA) and late antigens (LA) of HCMV. RESULTS: Twelve out of sixteen cases (75%) presented at least one HCMV antigen. Eight cases presented both antigens, three cases only the IEA and one case only the LA. These antigens were present in decidual cells, in stromal cells of chorionic villi and in trophoblastic cells. CONCLUSIONS: The results showed high frequency of HCMV antigens in tissues from first trimester abortion. This frequency, higher than that previously reported, was probably due to the fact that necro-inflammatory lesions were always present in selected cases. The presence of LA in trophoblastic cells is evidence for cell permissiveness to viral replication in vivo. The results showing high presence of HCMV antigens in tissues from abortion with inflammatory lesions suggest a possible relationship of HCMV infection with inflammation and pregnancy loss.