Analysis of humoral immune responses in rhesus macaques vaccinated with attenuated SIVmac239Deltanef and challenged with pathogenic SIVmac251.

BACKGROUND: To determine the correlation between protection and humoral immune response against simian immunodeficiency virus (SIVmac251), 11 macaques were immunized with live-attenuated SIVmac239Deltanef either intravenously or via the tonsils and exposed to SIVmac251 after either 6 or 15 months along with unvaccinated controls. RESULTS: Independent of the route of vaccine application, viremia was significantly reduced in vaccinees compared with controls 2 weeks post-challenge. Concomitantly, viremia correlated inversely with SIV-specific IgG, complement-mediated lysis and neutralizing antibodies and these parameters seemed to contribute to reduced viremia. During chronic infection, six monkeys controlled viremia in the circulation (two or fewer infectious units per 10(6) PBMCs) and showed no signs of trapping in lymphatic tissues (Appendix S1). CONCLUSIONS: As no significant differences were observed throughout the study, with respect to the humoral immune response and viremia control, between the two vaccinated cohorts, mucosal immunization strategies are recommended due to more simplified application.

Changes in HIV-specific antibody responses and neutralization titers in patients under ART.

In this study, we tested for antibody reactivities against gp120 and gp41-derived peptides, recombinant gp160, gp41 and tat in HIV-positive sera under antiretroviral therapy (ART) and determined their neutralization capacity. As a baseline, sera from patients in stage A, B and C of the disease, long term non-progressors (LNPs) and HIV-negative individuals were included. Compared to LNPs or sera from patients in group A, the reactivity of sera in stage B or C against gp120-derived peptides was reduced parallel to disease progression. Reactivity of these samples was compared with sera of patients under ART. Parallel to the decrease of viral load, the reactivity against gp120 and gp41-derived epitopes, recombinant gp160 and gp41 or the native gp120/41 complex was significantly reduced. Antibody-mediated neutralization of HIV-1 was detectable prior to ART but revealed substantial decreases coupled with progression of therapy. Responses to recombinant tat dropped after three months of therapy, increased however at later time points to initial levels. These data indicate that in parallel to the decrease in viral load and antibodies against gp120, the neutralization capacity of sera under ART is reduced, and can not be compensated by an increase in tat-specific antibodies.

Role of complement in the pathogenesis of SIV infection.

Lentiviruses have adapted several strategies to avoid complement-mediated lysis. Thus, interaction of HIV or SIVmac with complement proteins and the subsequent binding to complement receptor (CR) positive cells, leads to significant enhancement of infection. In addition, the trapping of viral antigens and intact infectious viruses on follicular dendritic cells in the lymphatic tissue is, in the case of HIV, strongly dependent on complement. In contrast, natural hosts of primate lentiviruses such as African green monkeys, Sooty mangabeys or Chimpanzees are resistant to the development of clinical AIDS despite persistent replication of SIV. In the present review interactions of lentiviruses with complement in different primate species and the possible consequences of such interactions for the progression to AIDS in different hosts are discussed.