The relationship of Plasmodium falciparum humeral immunity with HIV-1 immunosuppression and treatment efficacy in Zambia

Abstract

BackgroundHIV-1 infection affects malaria humeral immunity during pregnancy, but data for non-pregnant adults are lacking. This study reports the impact of HIV-1 infection and other variables on the level of malaria humeral immunity in adults with clinical malaria and whether humeral immune suppression was a risk factor for treatment failure.MethodsSera of 224 HIV-1 infected and 115 uninfected adults were compared for IgG to merozoite antigens AMA-1 and MSP2 (3D7 and FC27 types) determined by ELISA, and for IgG to the Variant Surface Antigens (VSA) of three different parasite line E8B, A4 and HCD6 determined by flow cytometry.ResultsCompared to HIV-1 uninfected adults, AMA-1 IgG was lower in HIV-1 infected (P = 0.02) and associated with low CD4 count AMA-1 IgG (P = 0.003). Low IgG to all three merozoite antigens was associated with less anemia (P = 0.03). High parasite load was associated with low MSP2 IgG 3D7 and FC27 types (P = 0.02 and P = 0.08). Antibody levels to VSA did not differ between HIV-1 infected and uninfected adults. However, low VSA IgGs were associated with high parasite load (P ≤ 0.002 for each parasite line) and with treatment failure (P ≤ 0.04 for each parasite line).ConclusionHIV-1 affects humeral responses to AMA-1, but seems to marginally or not affect humeral responses to other merozoite antigens and VSAs. The latter were important for controlling parasite density and predict treatment outcome.

Associations between Antibodies to a Panel of Plasmodium falciparum Specific Antigens and Response to Sub-Optimal Antimalarial Therapy in Kampala, Uganda

“…These studies have found associations between positive or high IgG responses to a number of antigens (NANP repeat of CSP [39], K1 and MAD20 block 2 variants of MSP-1 [34], MSP-1 19 [32], [33], and GLURP-R0 and R2 [36]) and protection from treatment failure. Three of these studies included assessment of AMA-1 antibodies in their analyses, but these did not show strong associations between anti-AMA-1 levels and clearance of parasitemia [33], [36], [37]. Differences between our results and prior studies may be attributable to the antimalarial therapy used, due to varying efficacy and pharmacokinetics; differences in the epidemiological setting and patient characteristics; different means of assessing treatment outcome; and the use of different laboratory and analytical methods.…”

Phase 1b Randomized Trial and Follow-Up Study in Uganda of the Blood-Stage Malaria Vaccine Candidate BK-SE36

“…Likewise, there are a number of confounding factors that also need to be taken into account (e.g. host genetic variation, host immune status) for the absence of antibody responses in some seronegative malaria-exposed subjects [29]. There was, however, no indication of general immune suppression correlated to race or genetic background since antibody responses were induced in malaria-naïve Japanese adults, the majority of seronegative Ugandan adults and young cohorts.…”

Interactions between malaria and human immunodeficiency virus anno 2014

“…Phagocytosis, proliferative and Th1 cytokine responses are reduced in pregnant women with HIV infection, and pregnancy may contribute to impaired control of malaria in HIV-infected individuals [ 8 ]. However, variant surface antigen antibody levels, which seem important for the control of parasite density and treatment outcome, seem to be marginally or not affected by HIV-1 in non-pregnant adults [ 9 ]. In pregnancy, although antimalarial antibody responses are mostly unaltered, there seem to be impaired responses to some antigens, including variant surface antigens expressed on infected erythrocytes binding chondroitin sulfate A, a key receptor for placental sequestration.…”