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The present study includes several works which have common goal to further clarify the humoral correlates of protection against HIV infection, present in those populations that naturally can remain IgG-seronegative, despite a long-term exposure to HIV (ESNs), or are able to control for a long time the same infection (LTNPs, ECs). In fact, the first part of the thesis is concerned about the study of protective humoral parameters which would characterize a cohort of 45 HIV-infected individuals at different clinical stages (10 AI, Acute Infection, 10 LTNPs, 8 ECs, 7 AIDS, 10 HAART +); a cohort consisting of South African mothers infected with HIV subtype C, coupled with their infants, some of which are seronegative (as a particular ESN group), and finally, a cohort of women in Cambodian ESN, whose B cells, in their cervicovaginal secretions, were used to construct a library of Fab IgA phage-k/?, which was screened for specificity to HIV-gp41. The results showed that heterogeneous humoral responses were observed in groups of HIV seropositive subjects. The high variability of total or gp41-specific IgA among all patients groups, supported their role as a biomarker. Infact, significant differences were detected in AI and in LTNP for IgA to gp41 and in IgG to gp120, respectively. Moreover, three domains of gp41, HR1, IDE and MPER, elicited antibodies that were effectively transmitted to ESN babies. In such babies, epitopes overlapping the 2F5 (ELDKWAS), but not the 4E10 epitope, were neutralization targets in two out of four viruses tested. Finally, the Fabs IgA from ESN women blocked efficiently transcytosis of HIV-1 with IC90 |
