Browsing by Author "Mubanga C"

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Application of a Novel Proteomic Microarray Reveals High Exposure to Diarrhoeagenic
(2024-Feb-20) Mwape K; Mubanga C; Chilyabanyama ON; Chibesa K; Chisenga CC; Silwamba S; Randall A; Liang X; Barnard TG; Simuyandi M; Chilengi R; Division of Medical Microbiology, Department of Pathology, Stellenbosch University & National Health Laboratory Service, Tygerberg Hospital Francie van Zijl Drive, P.O. Box 241, Cape Town 8000, South Africa.; Next Generation Sequencing Unit and Division of Virology, School of Pathology, Faculty of Health Sciences, University of the Free State, P.O. Box 339, Bloemfontein 9300, South Africa.; Department of Basic Medical Sciences, Michael Chilufya Sata School of Medicine, Copperbelt University, Ndola P.O. Box 71191, Zambia.; Water and Health Research Center, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg 2028, South Africa.; Enteric Disease and Vaccines Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; Antigen Discovery Inc., 1 Technology Dr., STE E309, Irvine, CA 92618, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Diarrhoeagenic
Effect of HIV status and retinol on immunogenicity to oral cholera vaccine in adult population living in an endemic area of Lukanga Swamps, Zambia.
(2021) Luchen CC; Mwaba J; Ng'ombe H; Alabi PIO; Simuyandi M; Chilyabanyama ON; Hatyoka LM; Mubanga C; Bosomprah S; Chilengi R; Chisenga CC; Amsterdam UMC, University of Amsterdam, Institute for Infection and Immunity, Amsterdam, the Netherlands.; Enteric Diseases and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; University of Zambia, School of Health Sciences, Lusaka, Zambia.
BACKGROUND: We set out to assess the impact of human immunodeficiency virus (HIV) and micronutrient deficiency as indicated by serum retinol levels on the immune responses to Oral Cholera Vaccine (Shanchol™) in a cohort of participants in Lukanga Swamps, Zambia. Cholera remains endemic in Zambia with vaccines being the only effective preventive measures. However, the effect of these vaccines on populations living with HIV has not been widely documented. METHODS: HIV testing and confirmation was done using the Alere Determine™ HIV-1/2 and Uni-Gold™ kits while vibriocidal antibody assay was applied for vaccine immunogenicity. Serum retinol analysis was assessed by Shimadzu Prominence HCT-2010 High Performance Liquid Chromatography (HPLC). The primary outcome was log transformed geometric mean titre. RESULTS: From 47 participants screened for HIV, 51% (24) tested positive. There was a statistically significant reduction in Ogawa geometric mean ratio (GMR) by 67% (GMR = 0.33; 95% CI: -0.15, 0.76; p-value = 0.009) attributable to HIV positivity with a non-significant reduction in Inaba GMR by about 50% due to HIV positivity. When doubling of retinol levels modelled, GMR reduction against Ogawa were non-significant but that against Inaba resulted in a significant reduction in geometric mean titer (GMT) (GMT-0.33, C.I 0.16-0.66, p-value 0.002). At 1000copies/ml viral load cut off and 350 cells/μl CD4 counts, Ogawa GMT was two times higher 11.16 (95%CI: 8.20-15.19) versus 6.06 (95%CI: 4.04-9.10) in low viremia participants, and three times higher in above threshold CD4 count participants; 24.81 (95%CI: 18.94-32.50) versus 7.07 (95%CI: 5.22-9.58). CONCLUSION: Our results show that while Shanchol™ is immunogenic in both HIV+/- individuals, HIV + participants responded poorly. Viral load and CD4 count affected vaccine immunogenicity. More research is required for detailed understanding of this in order to appropriately inform policy and practice.
Evaluation of ROTARIX
(2023-Feb-03) Laban NM; Bosomprah S; Simuyandi M; Chibuye M; Chauwa A; Chirwa-Chobe M; Sukwa N; Chipeta C; Velu R; Njekwa K; Mubanga C; Mwape I; Goodier MR; Chilengi R; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.; Department of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam University Medical Centers, University of Amsterdam, Paasheuvelweg 25, 1105 BP Amsterdam, The Netherlands.; Division of Medical Microbiology, Department of Pathology, Stellenbosch University & National Health Laboratory Service, Tygerberg Hospital Francie van Zijl Drive, Tygerberg, P.O. Box 241, Cape Town 8000, South Africa.; Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana.; Flow Cytometry and Immunology Facility, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine, Fajara, Banjul P.O. Box 273, The Gambia.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka P.O. Box 50110, Zambia.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Oral rotavirus vaccines show diminished immunogenicity in low-resource settings where rotavirus burden is highest. This study assessed the safety and immune boosting effect of a third dose of oral ROTARIX
Immunogenicity and waning immunity from the oral cholera vaccine (Shanchol™) in adults residing in Lukanga Swamps of Zambia.
(2022) Ng Ombe H; Simuyandi M; Mwaba J; Luchen CC; Alabi P; Chilyabanyama ON; Mubanga C; Hatyoka LM; Muchimba M; Bosomprah S; Chilengi R; Kwenda G; Chisenga CC; Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
INTRODUCTION: In cholera endemic areas, the periodicity of cholera outbreaks remains unpredictable, making it difficult to organize preventive efforts. Lack of data on duration of protection conferred by oral cholera vaccines further makes it difficult to determine when to deploy preemptive vaccination. We report on the immunogenicity and waning of immunity to Shanchol™ in Lukanga Swamps. METHODS: We enrolled a cohort of 223 participants aged between 18 and 65 years old from whom serum samples were collected at baseline, day 28 before administration of the second dose, and consecutively at 6, 12, 24, 30, 36, and 48 months. Vibriocidal antibody titres were measured and expressed as geometric mean titres. Box plots and 95% CI were computed at each visit for both Inaba and Ogawa. Seroconversion was defined as a four fold or greater increase in antibody titres compared to baseline titres. RESULTS: Overall, seroconversion against V. cholerae Inaba and Ogawa after 1st dose was 35/134 (26%) and 34/134 (25%) respectively. We observed a statistical difference in seroconversion between the two subgroups of baseline titres (low <80 and high ≥80) for both Inaba (p = 0.02) and Ogawa (p<0.0001). From a baseline of 13.58, anti-Ogawa GMT increased to 21.95 after the first dose, but rapidly waned to 14.52, 13.13, and 12.78 at months 6, 12 and 24 respectively, and then increased to 13.21, 18.67 and 23.65 at months 30, 36 and 48 respectively. A similar trend was observed for anti-Inaba GMT across the same time points. CONCLUSION: We found that Shanchol™ was immunogenic in our study population and that vibriocidal antibodies may not be a good marker for long-term immunity. The observed rise in titres after 36 months suggests natural exposure, and this may be a critical time window opening for natural transmission in an endemic areas. We recommend re-vaccination at this time point in high risk areas.
Maternal and Infant Histo-Blood Group Antigen (HBGA) Profiles and Their Influence on Oral Rotavirus Vaccine (Rotarix
(2023-Jul-31) Chauwa A; Bosomprah S; Laban NM; Phiri B; Chibuye M; Chilyabanyama ON; Munsaka S; Simuyandi M; Mwape I; Mubanga C; Chobe MC; Chisenga C; Chilengi R; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.; Department of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam University Medical Centers, University of Amsterdam, 1012 WP Amsterdam, The Netherlands.; Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka P.O. Box 50110, Zambia.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Live-attenuated, oral rotavirus vaccines have significantly reduced rotavirus-associated diarrhoea morbidity and infant mortality. However, vaccine immunogenicity is diminished in low-income countries. We investigated whether maternal and infant intrinsic susceptibility to rotavirus infection via histo-blood group antigen (HBGA) profiles influenced rotavirus (ROTARIX
Prevalence of Diarrhoeagenic
(2023-Nov-17) Mwape K; Bosomprah S; Chibesa K; Silwamba S; Luchen CC; Sukwa N; Mubanga C; Phiri B; Chibuye M; Liswaniso F; Somwe P; Chilyabanyama O; Chisenga CC; Muyoyeta M; Simuyandi M; Barnard TG; Chilengi R; Division of Medical Microbiology, Department of Pathology, Stellenbosch University & National Health Laboratory Service, Tygerberg Hospital Francie van Zijl Drive, P.O. Box 241, Cape Town 8000, South Africa.; Department of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.; Amsterdam Institute of Infection and Immunity, Amsterdam University Medical Centers, 1105 AZ Amsterdam, The Netherlands.; Department of Basic Medical Sciences, Michael Chilufya Sata School of Medicine, Copperbelt University, Ndola P.O. Box 71191, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana.; Next Generation Sequencing Unit and Division of Virology, Faculty of Health Sciences, University of the Free State, P.O. Box 339, Bloemfontein 9300, South Africa.; Enteric Disease and Vaccine Research Unit, Center for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; Water and Health Research Center, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein 2028, South Africa.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka P.O. Box 50110, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Diarrhoea is a major contributor to childhood morbidity and mortality in developing countries, with diarrhoeagenic
Safety, tolerability, and immunogenicity of an oral inactivated ETEC vaccine (ETVAX®) with dmLT adjuvant in healthy adults and children in Zambia: An age descending randomised, placebo-controlled trial.
(2023-Nov-02) Sukwa N; Mubanga C; Hatyoka LM; Chilyabanyama ON; Chibuye M; Mundia S; Munyinda M; Kamuti E; Siyambango M; Badiozzaman S; Bosomprah S; Carlin N; Kaim J; Sjöstrand B; Simuyandi M; Chilengi R; Svennerholm AM; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. Electronic address: nsofwa.sukwa@cidrz.org.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Division of Medical Microbiology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; Scandinavian Biopharma, Sweden.; Department of Microbiology and Immunology, University of Gothenburg, Sweden.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is an important cause of moderate to severe diarrhoea in children for which there is no licensed vaccine. We evaluated ETVAX®, an oral, inactivated ETEC vaccine containing four E. coli strains over-expressing the major colonization factors CFA/I, CS3, CS5, and CS6, a toxoid (LCTBA) and double mutant heat-labile enterotoxin (dmLT) adjuvant for safety, tolerability, and immunogenicity. METHODS: A double-blind, placebo-controlled, age-descending, dose-finding trial was undertaken in 40 adults, 60 children aged 10-23 months, and 146 aged 6-9 months. Adults received one full dose of ETVAX® and children received 3 doses of either 1/4 or 1/8 dose. Safety was evaluated as solicited and unsolicited events for 7 days following vaccination. Immunogenicity was assessed by evaluation of plasma IgA antibody responses to CFA/I, CS3, CS5, CS6, and LTB, and IgG responses to LTB. RESULTS: Solicited adverse events were mostly mild or moderate with only 2 severe fever reports which were unrelated to the vaccine. The most common events were abdominal pain in adults (26.7 % in vaccinees vs 20 % in placebos), and fever in children aged 6-9 months (44 % vs 54 %). Dosage, number of vaccinations and decreasing age had no influence on severity or frequency of adverse events. The vaccine induced plasma IgA and IgG responses against LTB in 100 % of the adults and 80-90 % of the children. In the 6-23 months cohort, IgA responses to more than 3 vaccine antigens after 3 doses determined as ≥2-fold rise was significantly higher for 1/4 dose compared to placebo (56.7 % vs 27.2 %, p = 0.01). In the 6-9 months cohort, responses to the 1/4 dose were significantly higher than 1/8 dose after 3 rather than 2 doses. CONCLUSION: ETVAX® was safe, tolerable, and immunogenic in Zambian adults and children. The 1/4 dose induced significantly stronger IgA responses and is recommended for evaluation of protection in children. CLINICAL TRIALS REGISTRATION: The trial is registered with the Pan African Clinical Trials Registry (PACTR Ref. 201905764389804) and a description of this clinical trial is available on: https://pactr.samrc.ac.za/Trial Design.
Sero-prevalence of arthropod-borne viral infections among Lukanga swamp residents in Zambia.
(2020) Chisenga CC; Bosomprah S; Musukuma K; Mubanga C; Chilyabanyama ON; Velu RM; Kim YC; Reyes-Sandoval A; Chilengi R; Department of Biostatistics, School of Public Health, University of Ghana, Accra.; The Jenner Institute, University of Oxford, The Henry Wellcome Building for Molecular Physiology, Oxford, England, United Kingdom.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
INTRODUCTION: The re-emergence of vector borne diseases affecting millions of people in recent years has drawn attention to arboviruses globally. Here, we report on the sero-prevalence of chikungunya virus (CHIKV), dengue virus (DENV), mayaro virus (MAYV) and zika virus (ZIKV) in a swamp community in Zambia. METHODS: We collected blood and saliva samples from residents of Lukanga swamps in 2016 during a mass-cholera vaccination campaign. Over 10,000 residents were vaccinated with two doses of Shanchol™ during this period. The biological samples were collected prior to vaccination (baseline) and at specified time points after vaccination. We tested a total of 214 baseline stored serum samples for IgG antibodies against NS1 of DENV and ZIKV and E2 of CHIKV and MAYV on ELISA. We defined sero-prevalence as the proportion of participants with optical density (OD) values above a defined cut-off value, determined using a finite mixture model. RESULTS: Of the 214 participants, 79 (36.9%; 95% CI 30.5-43.8) were sero-positive for Chikungunya; 23 (10.8%; 95% CI 6.9-15.7) for Zika, 36 (16.8%; 95% CI 12.1-22.5) for Dengue and 42 (19.6%; 95% CI 14.5-25.6) for Mayaro. Older participants were more likely to have Zika virus whilst those involved with fishing activities were at greater risk of contracting Chikungunya virus. Among all the antigens tested, we also found that Chikungunya saliva antibody titres correlated with baseline serum titres (Spearman's correlation coefficient = 0.222; p = 0.03). CONCLUSION: Arbovirus transmission is occurring in Zambia. This requires proper screening tools as well as surveillance data to accurately report on disease burden in Zambia.
Seroconversion and Kinetics of Vibriocidal Antibodies during the First 90 Days of Re-Vaccination with Oral Cholera Vaccine in an Endemic Population.
(2024-Apr-08) Chisenga CC; Phiri B; Ng'ombe H; Muchimba M; Musukuma-Chifulo K; Silwamba S; Laban NM; Luchen C; Liswaniso F; Chibesa K; Mubanga C; Mwape K; Simuyandi M; Cunningham AF; Sack D; Bosomprah S; Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.; Institute of Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individuals resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled and re-vaccinated with two doses of Shanchol™, regardless of previous vaccination, and followed-up for 90 days. Bloods were collected at baseline before re-vaccination, at day 14 prior to second dosing, and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60, and 90 days across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly, irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination.
The 2022 Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference: Summary of abstract-based presentations.
(2024-Mar-07) Banerjee S; Barry EM; Baqar S; Louis Bourgeois A; Campo JJ; Choy RKM; Chakraborty S; Clifford A; Deal C; Estrada M; Fleckenstein J; Hasso-Agopsowicz M; Hausdorff W; Khalil I; Maier N; Mubanga C; Platts-Mills JA; Porter C; Qadri F; Simuyandi M; Walker R; White JA; Washington University School of Medicine, United States.; PATH, United States. Electronic address: aclifford@path.org.; Centre for Infectious Disease Research in Zambia, Zambia.; Antigen Discovery, Inc, United States.; PATH, United States; Faculty of Medicine, Université Libre de Bruxelles, Belgium.; ICMR - National Institute of Cholera and Enteric Diseases, India.; PATH, United States.; Naval Medical Research Command, United States.; World Health Organization, Switzerland.; University of Washington, United States.; US National Institutes of Health, United States.; Johns Hopkins University, United States.; Division of Infectious Diseases and International Health, University of Virginia, United States.; ICDDR,B, Bangladesh.; University of Maryland School of Medicine, United States.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
The global nonprofit organization PATH hosted the third Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference in Washington, DC, on November 29 to December 1, 2022. With a combination of plenary sessions and posters, keynote presentations, and breakout workshops, the 2022 VASE Conference featured key updates on research related to the development of vaccines against neglected diarrheal pathogens including Shigella, enterotoxigenic Escherichia coli (ETEC), Campylobacter, and Salmonella. The presentations and discussions highlighted the significant impact of these diarrheal pathogens, particularly on the health of infants and young children in low- and middle-income countries, reflecting the urgent need for the development and licensure of new enteric vaccines. Oral and poster presentations at the VASE Conference explored a range of topics, including: the global burden and clinical presentation of disease, epidemiology, and the impact of interventions; the assessment of the value of vaccines against enteric pathogens; preclinical evaluations of vaccine candidates and models of enteric diseases; vaccine candidates in clinical trials and human challenge models; host parameters and genomics that predict responses to infection and disease; the application of new omics technologies for characterization of emerging pathogens and host responses; novel adjuvants, vaccine delivery platforms, and immunization strategies; and strategies for combination/co-administered vaccines. The conference agenda also featured ten breakout workshop sessions on topics of importance to the enteric vaccine field, which are summarized separately. This article reviews key points and highlighted research presented in each of the plenary conference sessions and poster presentations at the 2022 VASE Conference.
Use of an ETEC Proteome Microarray to Evaluate Cross-Reactivity of ETVAX
(2023-May-04) Mubanga C; Simuyandi M; Mwape K; Chibesa K; Chisenga C; Chilyabanyama ON; Randall A; Liang X; Glashoff RH; Chilengi R; Division of Medical Microbiology, Department of Pathology, Stellenbosch University & National Health Laboratory Service, Tygerberg Hospital Francie van Zijl Drive, P.O. Box 241, Cape Town 8000, South Africa.; Division of Virology, School of Pathology, Faculty of Health Sciences, University of the Free State, 205 Nelson Mandela, P.O. Box 339, Bloemfontein 9300, South Africa.; Antigen Discovery Inc., 1 Technology Dr., Suite E309, Irvine, CA 92618, USA.; Water and Health Research Center, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein 2028, South Africa.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Developing a broadly protective vaccine covering most ETEC variants has been elusive. The most clinically advanced candidate yet is an oral inactivated ETEC vaccine (ETVAX