Browsing by Author "Nalwoga, Angela"

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    Association between malaria exposure and Kaposi’s sarcoma-associated herpes virus seropositivity in Uganda
    (Tropical medicine & international health, 2015) Nalwoga, Angela; Cose, Stephen; Wakeham, Katie; Miley, Wendell; Ndibazza, Juliet; Drakeley, Christopher; Elliott, Alison; Whitby, Denise; Newton, Robert
    Unlike other herpes viruses, Kaposi’s sarcoma-associated herpes virus (KSHV) is not ubiquitous worldwide and is most prevalent in sub-Saharan Africa. The reasons for this are unclear. As part of a wider investigation of factors that facilitate transmission in Uganda, a high prevalence country, we examined the association between antimalaria antibodies and seropositivity against KSHV. Antibodies against P. falciparum merozoite surface protein (PfMSP)-1, P. falciparumapical membrane antigen (PfAMA)-1 and KSHV antigens (ORF73 and K8.1) were measured in samples from 1164 mothers and 1227 children. results Kaposi’s sarcoma-associated herpes virus seroprevalence was 69% among mothers and 15% children. Among mothers, KSHV seroprevalence increased with malaria antibody titres: from 60% to 82% and from 54% to 77%, comparing those with the lowest and highest titres for PfMSP- 1 and PfAMA-1, respectively (P < 0.0001). Among children, only antibodies to PfAMA-1 were significantly associated with KSHV seropositivity, (P < 0.0001). In both mothers and children, anti- ORF73 antibodies were more strongly associated with malaria antibodies than anti-K8.1 antibodies. conclusion The association between malaria exposure and KSHV seropositivity suggests that malaria is a cofactor for KSHV infection or reactivation.
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    The Effect of Current Schistosoma Mansoni Infection on the Immunogenicity of A Candidate TB vaccine, MVA85A, in BCG Vaccinated Adolescents: An open-label trial
    (PLoS neglected tropical diseases, 2017) Wajja, Anne; Kizito, Dennison; Nassanga, Beatrice; Nalwoga, Angela; Kabagenyi, Joyce; Kimuda, Simon; Galiwango, Ronald; Mutonyi, Gertrude; Vermaak, Samantha; Tukahebwa, Edridah; McShane, Helen
    Helminth infection may affect vaccine immunogenicity and efficacy. Adolescents, a target population for tuberculosis booster vaccines, often have a high helminth burden. We investigated effects of Schistosoma mansoni (Sm) on the immunogenicity and safety of MVA85A, a model candidate tuberculosis vaccine, in BCG-vaccinated Ugandan adolescents.In this phase II open label trial we enrolled 36 healthy, previously BCG-vaccinated adolescents, 18 with no helminth infection detected, 18 with Sm only. The primary outcome was immunogenicity measured by Ag85A-specific interferon gamma ELISpot assay. Tuberculosis and schistosome-specific responses were also assessed by whole-blood stimulation and multiplex cytokine assay, and by antibody ELISAs.Ag85A-specific cellular responses increased significantly following immunisation but with no differences between the two groups. Sm infection was associated with higher pre-immunisation Ag85A-specific IgG4 but with no change in antibody levels following immunisation. There were no serious adverse events. Most reactogenicity events were of mild or moderate severity and resolved quickly.The significant Ag85A-specific T cell responses and lack of difference between Sm-infected and uninfected participants is encouraging for tuberculosis vaccine development. The implications of pre-existing Ag85A-specific IgG4 antibodies for protective immunity against tuberculosis among those infected with Sm are not known. MVA85A was safe in this population.
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    Mycobacterium Tuberculosis Infection Boosts B Cell 2 Responses to Unrelated Pathogens
    (bioRxiv, 2019) Kimuda, Simon G.; Andia-Biraro, Irene; Sebina, Ismail; Egesa, Moses; Nalwoga, Angela; Bagaya, Bernard S.; Elliott, Alison M.; Cose, Stephen
    Antigens from Mycobacterium tuberculosis (M.tb), have been shown to stimulate human B cell responses to unrelated recall antigens in vitro. However, it is not known whether natural M.tb infection or whether vaccination with the related species, Mycobacterium bovis BCG, has a similar effect. This study investigated the effects of M.tb infection and BCG vaccination on B cell responses to heterologous pathogen recall antigens. Antibodies against several bacterial and viral pathogens were quantified by ELISA in 68 uninfected controls, 62 individuals with latent TB infection (LTBI) and 107 active pulmonary TB (APTB) cases, and 24 recently BCG-vaccinated adolescents and naive controls. Antibody avidity was investigated using surface plasmon resonance and B cell ELISPOT assays were used to measure plasmablast and memory B cell responses (MBC) in APTB cases and healthy donor controls. APTB was associated with higher levels of antibodies to tetanus toxoid (TT), diphtheria toxoid, respiratory syncytial virus, measles virus and Kaposi’s sarcoma herpesvirus, compared to uninfected controls. Vaccination with BCG did not alter levels of antibodies against heterologous pathogens. TT-specific antibody avidity was increased in APTB and the ratio of TT-specific plasmablasts to MBCs in the APTB cases was 7:1. M.tb infection boosts serological memory to heterologous pathogens in human subjects and this process may be driven by polyclonal activation of memory B cells.
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    Mycobacterium Tuberculosis Infection is Associated with Increased B Cell Responses to Unrelated Pathogens
    (Scientific reports, 2020) Kimuda, Simon G.; Andia‑Biraro, Irene; Sebina, Ismail; Egesa, Moses; Nalwoga, Angela; Smith, Steven G.; Bagaya, Bernard S.; Levin, Jonathan; Elliott, Alison M.; Cose, Stephen
    Antigens from Mycobacterium tuberculosis (M.tb), have been shown to stimulate human B cell responses to unrelated recall antigens in vitro. However, it is not known whether natural M.tb infection or whether vaccination with, Mycobacterium bovis BCG, has a similar efect. This study investigated the efects of M.tb infection and BCG vaccination on B cell responses to heterologous pathogen recall antigens. Antibodies against several bacterial and viral pathogens were quantifed by ELISA in 68 uninfected controls, 62 individuals with latent TB infection (LTBI) and 107 active pulmonary TB (APTB) cases, and 24 recently BCG-vaccinated adolescents and naive controls. Antibody avidity was investigated using surface plasmon resonance and B cell ELISPOTs were used to measure plasmablast and memory B cell responses (MBC) in APTB cases and healthy donor controls. APTB was associated with higher levels of antibodies to respiratory syncytial virus and measles virus, compared to uninfected controls. BCG vaccination did not alter levels of antibodies against heterologous pathogens. Tetanus toxoid (TT)-specifc antibody avidity was increased in APTB cases in comparison to uninfected individuals and the ratio of TT-specifc plasmablasts to MBCs in the APTB cases was 7:1. M.tb infection is associated with increased antibody responses to heterologous pathogens in human subjects.
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    Profiles of Inflammatory Markers and their Association With Cardiometabolic Parameters in Rural and Urban Uganda
    (Wellcome Open Research, 2021) Sanya, Richard E.; Nalwoga, Angela; Grencis, Richard K.; Elliott, Alison M.; Webb, Emily L.; Biraro, Irene Andia
    Inflammation may be one of the pathways explaining differences in cardiometabolic risk between urban and rural residents. We investigated associations of inflammatory markers with rural versus urban residence, and with selected cardiometabolic parameters previously observed to differ between rural and urban residents: homeostatic model assessment of insulin resistance (HOMA-IR), fasting blood glucose (FBG), blood pressure (BP) and body mass index (BMI).From two community surveys conducted in Uganda, 313 healthy individuals aged ≥ 10 years were selected by age- and sex-stratified random sampling (rural Lake Victoria island communities, 212; urban Entebbe municipality, 101). Fluorescence intensities of plasma cytokines and chemokines were measured using a bead-based multiplex immunoassay. We used linear regression to examine associations between the analytes and rural-urban residence and principal component analysis (PCA) to further investigate patterns in the relationships. Correlations between analytes and metabolic parameters were assessed using Pearson’s correlation coefficient.The urban setting had higher mean levels of IL-5 (3.27 vs 3.14, adjusted mean difference [95% confidence interval] 0.12[0.01,0.23] p=0.04), IFN-⍺ (26.80 vs 20.52, 6.30[2.18,10.41] p=0.003), EGF (5.67 vs 5.07, 0.60[0.32,0.98] p<0.00001), VEGF (3.68 vs 3.28, 0.40[0.25,0.56] p<0.00001), CD40 Ligand (4.82 vs 4.51, 0.31[0.12, 0.50] p=0.001) and Serpin-E1 (9.57 vs 9.46, 0.11[0.05,0.17] p<0.00001), but lower levels of GMCSF (2.94 vs 3.05, -0.10[-0.19,-0.02] p=0.02), CCL2 (2.82 vs 3.10, -0.45[-0.70,-0.21] p<0.00001) and CXCL10 (5.48 vs 5.96, -0.49[-0.71,-0.27] p<0.00001), compared to the rural setting. In PCA, the urban setting had lower representation of some classical inflammatory mediators but higher representation of various chemoattractants and vasoactive peptides. HOMA-IR, FBG, BP and BMI were positively correlated with several principal components characterised by pro-inflammatory analytes.In developing countries, immunological profiles differ between rural and urban environments. Differential expression of certain pro-inflammatory mediators may have important health consequences including contributing to increased cardiometabolic risk observed in the urban environment.
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    Risk Factors for Seropositivity to Kaposi Sarcoma–Associated Herpesvirus Among Children in Uganda
    (Journal of acquired immune deficiency syndromes, 2013) Wakeham, Katie; Webb, Emily L.; Sebina, Ismail; Nalwoga, Angela; Muhangi, Lawrence; Miley, Wendell; Johnston, W. Thomas; Ndibazza, Juliet; Whitby, Denise; Newton, Robert; Elliott, Alison M.
    Determinants of Kaposi sarcoma–associated herpesvirus (KSHV) seropositivity among children living in sub-Saharan African populations where infection is endemic are not well understood. Local environmental factors, including other infectious agents, may be key. Within the context of a well-characterized birth cohort, we examined associations between various factors and antibodies against KSHV, measured in stored plasma samples from 1823 mother–child pairs in Entebbe, Uganda.