The EDCTP Alumni Network

Dr
Caroline Chisenga

Related fellows

Associate Professor Richard Phillips

Scientific Director (KCCR), Associate Professor of Medicine

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Dr ADOUAKA Gaetan Robert

Etudiant en Master

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Dr Debora Kajeguka

Senior Lecturer

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Profile EDCTP Fellowship 1

Project Title

Immunogenicity to cholera vaccine within a population at risk in Zambia: mapping the kinetics of immune responses over time

EDCTP Project

TMA2016CDF1550

EDCTP Program

EDCTP2

EDCTP Project Call

Career Development Fellowship (CDF)

Project Objectives

• Determine cholera specific antibody titers at baseline (prior vaccination) • Determine seroconversion after 1st and 2nd doses • Asses benefits of a 2nd dose of OCV given after 4 weeks following the 1st dose • Determine if vaccine immune responses wane off at 6, 12, 24, 36, 42 or 48 months post second dose OVC

Study Design

This is a pre/post-vaccine study involving a cohort of individuals receiving an oral cholera vaccine provided by the ministry of health (MoH) in response to a cholera outbreak in the Lukanga Swamps. Volunteering eligible individuals were, consented, enrolled and the questionnaire administered.

Project Summary

In LMIC, oral vaccines perform poorly and several reasons are postulated including maternal breast milk components, environmental enteropathy, nutritional factors, and intestinal infections. Zambia has had a high burden of cholera over the past several years and the government is deploying a new oral cholera vaccine (Shanchol® manufactured by Shantha Biotechnics, India). While the vaccine has good efficacy in clinical trials, its real world immunogenicity is unproven. For example, the duration of vaccine induced immune response is not well characterized in LMICs where cholera outbreaks are common, the impact of human genetic predisposition on susceptibility to cholera on vaccine responses and the impact of HIV infection (which is common in Zambia) on the functional immune protection is unknown.

Host Organisation

Department	Institution	Country
Enteric Disease and Vaccine Research Unit	Centre for Infectious Disease Research in Zambia (CIDRZ)	Zambia

Sites

Lukanga Swamps-Central Province of Zambia

Results & Outcomes

In progress

Current Organisation

Centre for Infectious Disease Research in Zambia

Current Job Title

Research Fellow

Biography

Publications

Authors:

Luchen CC

Journal:

Plosone

Content:

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.

Date:

2021-12-02

Authors:

Natasha Makabilo Laban Samuel Bosomprah Kalo Musukuma-Chifulo Michelo Simuyandi Shilpa Iyer Harriet Ng'ombe Mutinta Muchimba Adriace Chauwa Sekayi Tigere Caroline Cleopatra Chisenga Mwelwa Chibuye Obvious Nchimunya Chilyabanyama Martin Goodier Roma Chilengi

Journal:

Content:

Date:

2021-05-06

Authors:

Harriet Ngombe

Journal:

Plosone

Content:

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.

Date:

2022-01-05

Authors:

Caroline C. Chisenga Ray Borrow Samuel Bosomprah Michelo Simuyandi Katayi Mwila-Kazimbaya Obvious N. Chilyabanyama Natasha M. Laban Anya Bialik Valeria Asato Shiri Meron-Sudai Gad Frankel Daniel Cohen Roma Chilengi

Journal:

PLOS ONE

Content:

Date:

2021-05-27

Authors:

Caroline C. Chisenga Abdallah M. Samy Samuel Bosomprah Kalo Musukuma Cynthia Mubanga Obvious N. Chilyabanyama Rachel M. Velu Young Chan Kim Arturo Reyes-Sandoval Roma Chilengi

Journal:

PLOS ONE

Content:

Date:

2020-07-01

Dr Caroline Chisenga

Related fellows

Associate Professor Richard Phillips

Dr ADOUAKA Gaetan Robert

Dr Debora Kajeguka

Project Title

EDCTP Project

EDCTP Program

EDCTP Project Call

Project Objectives

Study Design

Project Summary

Host Organisation

Sites

Results & Outcomes

Current Organisation

Current Job Title

Biography

Publications

Background

Methods

Results

Conclusion

Introduction

Methods

Results

Conclusion

Dr
Caroline Chisenga