Browsing by Author "Mwape, Kapambwe"

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Application of a Novel Proteomic Microarray Reveals High Exposure to Diarrhoeagenic Escherichia coli among Children in Zambia Participating in a Phase I Clinical Trial
(2024-2-20) Mwape, Kapambwe; Mubanga, Cynthia; Chilyabanyama, Obvious N.; Chibesa, Kennedy; Chisenga, Caroline C.; Silwamba, Suwilanji; Randall, Arlo; Liang, Xiaowu; Barnard, Tobias G.; Simuyandi, Michelo; Chilengi, Roma
Diarrhoeagenic E. coli (DEC) significantly contributes to the burden of diarrhoea among children. Currently, there is no approved vaccine against DEC, but several vaccines against the enterotoxigenic E. coli (ETEC) pathotype are in advanced clinical trial stages, including the ETVAX® vaccine, undergoing evaluation in Zambia. This study reports on the reactivity of antibodies from ETVAX® vaccine and placebo recipients in a phase I clinical trial to proteins derived from (DEC) other than ETEC. Plasma samples collected at two time points (prior to any vaccination and post-third dose vaccination) from 16 vaccinated and 4 placebo participants in a phase 1 clinical trial examining the safety, tolerability, and immunogenicity of ETVAX® with dmLT adjuvant were evaluated for IgG response to E. coli antigens other than ETEC using the Pan-DEC protein microarray. This was the first field application of the novel pan-DEC array as a new tool in assessing the antigenic breadth of antibody responses induced by the ETVAX vaccine, as well as to assess early life exposure to DEC pathotypes and other bacterial enteric pathogens. We observed that plasma obtained from ETVAX® and placebo recipients had high antibody reactivity to Ipa, SseC and EspB proteins. These findings suggest that there is high exposure early in life to DEC pathogens, like EPEC, EHEC, EAEC and EIEC in addition to ETEC, in the Zambian population. These immunological observations are consistent with the results of recent epidemiological studies assessing the etiology of diarrheal disease among infants and young children in Zambia.
Prevalence of Diarrhoeagenic Escherichia coli among Children Aged between 0-36 Months in Peri-Urban Areas of Lusaka
(2023-Nov-17) Mwape, Kapambwe; Bosomprah, Samuel; Chibesa, Kennedy; Silwamba, Suwilanji ; Luchen, Charlie C.; Sukwa, Nsofwa; Mubanga, Cynthia; Phiri, Bernard ; Chibuye, Mwelwa; Liswaniso, Fraser; Somwe, Paul; Chilyabanyama, Obvious; Chisenga, Caroline C.; Muyoyeta, Monde; Simuyandi, Michelo; Barnard, Tobias G.; Chilengi, Roma
Diarrhoea is a major contributor to childhood morbidity and mortality in developing countries, with diarrhoeagenic
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, Caroline C.; Phiri, Bernard; Ng'ombe, Harriet; Muchimba, Mutinta; Musukuma-Chifulo, Kalo; Silwamba, Suwilanji; Laban, Natasha M.; Luchen, Chaluma; Liswaniso, Fraser; Chibesa, Kennedy; Mubanga, Cynthia; Mwape, Kapambwe; Simuyandi, Michelo; Cunningham, Adam F.; Sack, David; Bosomprah, Samuel
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.
Use of an ETEC Proteome Microarray to Evaluate Cross-Reactivity of ETVAX Vaccine-Induced IgG Antibodies in Zambian Children
(2023-May-04) Mubanga, Cynthia; Simuyandi, Michelo; Mwape, Kapambwe ; Chibesa, Kennedy; Chisenga, Caroline C.; Chilyabanyama, Obvious N.; Randall, Arlo; Liang, Xiaowu; Glashoff, Richard H.; Chilengi, Roma
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
Use of an ETEC Proteome Microarray to Evaluate Cross-Reactivity of ETVAX® Vaccine-Induced IgG Antibodies in Zambian Children
(2023-5-4) Mubanga, Cynthia; Simuyandi, Michelo; Mwape, Kapambwe; Chibesa, Kennedy; Chisenga, Caroline C.; Chilyabanyama, Obvious N.; Randall, Arlo; Liang, Xiaowu; Glashoff, Richard H.; Chilengi, Roma
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®). We report on the use of a proteome microarray for the assessment of cross-reactivity of anti-ETVAX® IgG antibodies against over 4000 ETEC antigens and proteins. We evaluated 40 (pre-and post-vaccination) plasma samples from 20 Zambian children aged 10–23 months that participated in a phase 1 trial investigating the safety, tolerability, and immunogenicity of ETVAX® adjuvanted with dmLT. Pre-vaccination samples revealed high IgG responses to a variety of ETEC proteins including classical ETEC antigens (CFs and LT) and non-classical antigens. Post-vaccination reactivity to CFA/I, CS3, CS6, and LTB was stronger than baseline among the vaccinated compared to the placebo group. Interestingly, we noted significantly high post-vaccination responses to three non-vaccine ETEC proteins: CS4, CS14, and PCF071 (p = 0.043, p = 0.028, and p = 0.00039, respectively), suggestive of cross-reactive responses to CFA/I. However, similar responses were observed in the placebo group, indicating the need for larger studies. We conclude that the ETEC microarray is a useful tool for investigating antibody responses to numerous antigens, especially because it may not be practicable to include all antigens in a single vaccine.