ABSTRACT
BACKGROUND: Globally, approximately three million children die each year from vaccine preventable infectious diseases mainly in developing countries. Despite the success of the expanded immunization program, not all infants and children around the world develop the same protective immune response to the same vaccine. A vaccine must induce a response over the basal immune response that may be driven by population-specific, environmental or socio-economic factors. Mycotoxins like aflatoxins are immune suppressants that are confirmed to interfere with both cell-mediated and acquired immunity. The mechanism of aflatoxin toxicity is through the binding of the bio-activated AFB1-8, 9-epoxide to cellular macromolecules. METHODS: We studied Hepatitis B surface antibodies [anti-HBs] levels to explore the immune modulation effects of dietary exposure to aflatoxins in children aged between one and fourteen years in Kenya. Hepatitis B vaccine was introduced for routine administration for Kenyan infants in November 2001. To assess the effects of aflatoxin on immunogenicity of childhood vaccines Aflatoxin B1-lysine in blood serum samples were determined using High Performance Liquid Chromatography with Fluorescence detection while anti-HBs were measured using Bio-ELISA anti-HBs kit. RESULTS: The mean ± SD of AFB1-lysine adducts in our study population was 45.38 ± 87.03 pg/mg of albumin while the geometric mean was 20.40 pg/mg. The distribution of AFB1-lysine adducts was skewed to the right. Only 98/205 (47.8%) of the study population tested positive for Hepatitis B surface antibodies. From regression analysis, we noted that for every unit rise in serum aflatoxin level, anti-HBs dropped by 0.91 mIU/ml (-0.9110038; 95% C.I -1.604948, -0.21706). CONCLUSION: Despite high coverage of routine immunization, less than half of the study population had developed immunity to HepB. Exposure to aflatoxin was high and weakly associated with low anti-HBs antibodies. These findings highlight a potentially significant role for environmental factors that may contribute to vaccine effectiveness warranting further research.
Subject(s)
Aflatoxins/immunology , Hepatitis B Antibodies/blood , Hepatitis B Vaccines/immunology , Adolescent , Aflatoxins/blood , Albumins/analysis , Child , Child, Preschool , Cross-Sectional Studies , Cytokines/blood , Female , Humans , Infant , Kenya , Logistic Models , MaleABSTRACT
The impact of topical antiretrovirals for pre-exposure prophylaxis on humoral responses following HIV infection is unknown. Using a binding antibody multiplex assay, we investigated HIV-specific IgG and IgA responses to envelope glycoproteins, p24 Gag and p66, in the genital tract (GT) and plasma following HIV acquisition in women assigned to tenofovir gel (n=24) and placebo gel (n=24) in the CAPRISA 004 microbicide trial to assess if this topical antiretroviral had an impact on mucosal and systemic antibody responses. Linear mixed effect modeling and partial least squares discriminant analysis was used to identify multivariate antibody signatures associated with tenofovir use. There were significantly higher response rates to gp120 Env (P=0.03), p24 (P=0.002), and p66 (P=0.009) in plasma and GT in women assigned to tenofovir than placebo gel at multiple time points post infection. Notably, p66 IgA titers in the GT and plasma were significantly higher in the tenofovir compared with the placebo arm (P<0.05). Plasma titers for 9 of the 10 HIV-IgG specificities predicted GT levels. Taken together, these data suggest that humoral immune responses are increased in blood and GT of individuals who acquire HIV infection in the presence of tenofovir gel.
Subject(s)
Anti-Retroviral Agents/therapeutic use , Genitalia, Female/drug effects , HIV Antibodies/metabolism , HIV Infections/drug therapy , HIV-1/immunology , Immunoglobulin A/metabolism , Tenofovir/therapeutic use , Administration, Topical , Adult , Female , Follow-Up Studies , Genitalia, Female/immunology , Genitalia, Female/metabolism , HIV Core Protein p24/immunology , HIV Envelope Protein gp120/immunology , HIV Infections/immunology , HIV Reverse Transcriptase/immunology , Humans , Immunoglobulin G/metabolism , Treatment Outcome , Vaginal Creams, Foams, and Jellies , Young AdultABSTRACT
OBJECTIVE: To understand the pattern of immune responses to pneumococcal proteins during invasive disease as a guide to their development as vaccine candidates. METHODS: The antibody concentration and avidity, as well as frequency of interferon-gamma (IFN-γ)-, interleukin-10 (IL-10)-, and tumor necrosis factor-alpha (TNF-α)-containing CD4+ T-lymphocytes in response to pneumolysin, pneumococcal surface protein A (PspA), and choline-binding protein A (CbpA), during and after invasive pneumococcal disease (IPD) in 20 children were compared to those of 20 healthy matched controls. RESULTS: During the acute phase of IPD, the concentrations of antibodies against these three pneumococcal proteins were lower, whereas the frequencies of IL-10- and TNF-α-producing CD4+ T-cells were higher, compared to values obtained during convalescence and in healthy controls (p < 0.01). In addition, the concentrations of antibodies against the capsular polysaccharides for the serotypes isolated from these patients, were all below the detection level of the assay during both the acute and convalescent phases of IPD. CONCLUSION: These data indicate that the recognition of these antigens by the immune system occurs in variable proportions according to the stage of infection, implying the important role of these in the pathogenesis of IPD, and support their usefulness in vaccine development.
