Cervical cancer is a public health concern as it represents the second cause of cancer death in women worldwide. High-risk human papillomaviruses (HPV) are the etiologic agents, and HPV E6 and/or E7 oncogene-specific therapeutic vaccines are under development to treat HPV-related lesions in women. Whether the use of mucosal routes of immunization may be preferable for inducing cell-mediated immune responses able to eradicate genital tumors is still debated because of the uniqueness of the female genital mucosa (GM) and the limited experimentation. Here, we compared the protective activity resulting from immunization of mice via intranasal (i.n.), intravaginal (IVAG) or subcutaneous (s.c.) routes with an adjuvanted HPV type 16 E7 polypeptide vaccine. Our data show that s.c. and i.n. immunizations elicited similar frequencies and avidity of TetE7
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CD81 and E7-specific Interferon-gamma-secreting cells in the GM, whereas slightly lower immune responses were induced by IVAG immunization. In a novel orthotopic murine model, both s.c. and i.n. immunizations allowed for complete long-term protection against genital E7-expressing tumor challenge. However, only s.c. immunization induced complete regression of already established genital tumors. This suggests that the higher E7-specific systemic response observed after s.c. immunization may contribute to the regression of growing genital tumors, whereas local immune responses may be sufficient to impede genital challenges. Thus, our data show that for an efficiently adjuvanted protein-based vaccine, parenteral vaccination route is superior to mucosal vaccination route for inducing regression of established genital tumors in a murine model of HPV-associated genital cancer.Vaccination strategies that elicit cell-mediated immunity in the genital mucosa (GM) may be critical for protection against pathogens that use this mucosa as entry and replication site. This may be especially relevant in the case of genital human papillomavirus (HPV), as persistent infection with the high-risk types, most often HPV type 16 (HPV16), may lead to malignant diseases, including cervical cancer, 1 the second leading cause of cancer death in women worldwide.2 The available prophylactic vaccines prevent HPV infections through the induction of neutralizing antibodies, but they possess no therapeutic effects on already established HPV infections or associated lesions.3 Control of these lesions by cell-mediated immune responses is demonstrated by their increased prevalence when cell-mediated immunity is impaired [4][5][6] and by the finding that early infiltration of highly cytotoxic effector T cells in low-grade genital lesions appears to provide protection against tumor progression. 7 Thus, induction of cell-mediated immune responses against the HPV oncogenes (E6 and/or E7), which are implicated in initiation and maintenance of high-grade anogenital lesions, became an attractive approach, though with limited clinical success to date. 8 The most promising results [i.e., 47% regression of vulvar int...
Species of Haemoproteus (Haemoproteidae, Haemosporida) are common bird pathogens. Recent molecular studies combined with histopathology research have reported development of megalomeronts of these parasites in various organs, sometimes resulting in the death of the avian host. Five Common starlings (Sturnus vulgaris) were found naturally infected with Haemoproteus pastoris lineage hLAMPUR01. The parasite was identified using microscopic examination of blood films and DNA sequences. Infected bird organs were investigated histologically for (i) the presence of exo-erythrocytic stages and (ii) the patterns of development (morphology and localization) in different host individuals. For the first time, megalomeronts of Haemoproteus parasites were seen developing in the brain, while numerous others at different stages of maturation were found in the intestine, pancreas, kidneys, lungs, esophagus, spleen, gizzard, and trachea. Megalomeronts were predominantly roundish or oval, up to 800 μm, they were surrounded by a capsular-like wall and developed asynchronously in the same bird individual. After megalomeront maturation and rupture, a massive infiltration of blood cells occurred, indicating the hemorrhagic processes. Review of available data showed that different Haemoproteus species produce markedly different megalomeronts, morphology of which can probably be predicted using phylogenetic analysis based on partial sequences of cytochrome b gene.
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