View All Abstracts for Session 27
148 Helminthic Infections Have a Major Impact on Pathogenesis of AIDS and Success of HIV Vaccines
Z. Bentwich*, A. Kalinkovich, G. Borkow, M. Stein, L. Quibin, and Z. Weisman
Hebrew Univ.-Hadassah Med. Sch., Rehovot, Israel
Background: Helminthic infections cause chronic immune activation of the host that makes him more susceptible to HIV infection, less able to cope with it, and impaired in cellular immunity toward it. These effects may have a major impact on the pathogenesis of AIDS in Africa and other developing countries. The study of Ethiopian immigrants in Israel (ETI), Ethiopians in Ethiopia (ET), and non-Ethiopians in Israel (IS), enabled us to test this hypothesis.
Methods: Several groups of ETI, ET, and IS infected and noninfected by helminths and HIV were studied sequentially, clinically, and immunologically and by multivariate analysis before and after helminth eradication.
Results: (1) Helminthic infections induce a state of chronic immune activation with marked changes in the immune profile: (a) low levels of CD4, CD4/CD8 ratio, naive, and CD8/28 cells, increased levels of CD8 and memory cells, and increased apoptosis; (b) up-regulation of all immune activation markers-HLADR, CD8CD38, Ki67, and CTLA-4; (c) generalized anergy with decreased proliferative response to antigens, including loss of skin reactivity to PPD; (d) dominant TH2 cytokine immune profile. (2) Eradication of helminths, independent of changes in nutrition and environment, is followed by gradual return of the immune profile to normal values, including return of skin reactivity to PPD. (3) PBMC of ETI are more susceptible to HIV infection and have increased expression of CCR5 and CXCR4 coreceptors and decreased beta chemokine secretion.
Conclusions: (I) Helminthic infections have a profound impact on the host’s immunity due to the chronic immune activation they cause. (II) The immune activation makes the host more susceptible to HIV infection and impaired in the generation of cellular immunity, as well as less able to cope with HIV infection. (III) The anergy caused by the chronic immune activation may also result in impaired ability to immune reconstitution following HAART. (IV) The impaired host immunity may undermine the efficacy of HIV protective vaccine. (V) Development and trial of HIV vaccines in developing countries must take into account host background immunity and eradication of helminths before being widely applied.
Contact Author about this Abstract
