A Study of Intranasal Live Attenuated Influenza Vaccine Immunogenicity and Associations with the Nasopharyngeal Microbiome Among Children in the Gambia (NASIMMUNE)
This is a Wellcome Trust Intermediate Clinical Fellowship awarded to Dr deSilva. Using a systems biology approach within a clinical trial, the project investigates the mechanisms underlying varying level of immune responses to the live attenuated influenza vaccine (LAIV) in young children over two flu seasons. Over 300 children aged 24 -59 months are being recruited in order to find out what might determine the differences in vaccine efficacy observed between sub-saharan Africa and Europe.
Exploring mucosal molecular signatures associated with successful challenge with live attenuated influenza viruses
For this study various methods of RNA extraction from nasopharyngeal samples will be optimized. A pilot study will then examine which of the methods is best suited to generate RNAseq data from such samples. Further analysis with synthetic absorptive matrix (SAM) will be carried out by collaborators once the methods have been shared.
Nasopharyngeal samples from the NASIMMUNE study will be used to generate the RNAseq data. These samples were taken before and after live attenuated influenza vaccine was administered. The data along with RNAseq data from mucosal samples from collaborating sites will then be analysed.
Assessing Group Streptococcal Pyoderma in The Gambia (SPYDERM)
This study will examine skin infections due to Group A streptococcus (pyoderma) in children under the age of 5. It will look at how common such skin disease occurs in children in this age and determine whether they also have scabies. Scabies is common in young children and Group A streptococcus can affect the rash caused by scabies. Skin infections with Group A strep might be linked to heart disease, just as GAS in sore throats, and that prevention of GAS infections could lead to a reduction in rheumatic heart disease in The Gambia.
Site-preparedness and acceptancy of vaccines to be given in pregnancy- a WAGHA project
The project investigates the preparedness of women, health systems and health care workers to accept and administer vaccination in pregnancy in The Gambia and Senegal, using a mixed methods approach. It explores the attitudes and beliefs towards maternal immunisation through qualitative research and focus group interviews with pregnant women, women who delivered and their health care providers within urban and rural populations and health care settings in both countries.
EPIC-HIPC: Systems Biology to Identify Biomarkers of Neonatal Vaccine Immunogenicity
This systems-biology-based project will describe the innate immune signatures elicited by specific vaccines given to neonates while examining the hypothesis that early “omic” signatures can predict vaccine immunogenicity. Cutting-edge “omics” tools are applied to small volume blood samples from neonates to understand the impact of maturation of the immune system and vaccines in the first week of life. New bioinformatics and parallel in vitro approaches are being developed with partners at Harvard and University of British Columbia to integrate and interpret these complex datasets. A validation cohort will also be recruited in Papua-New Guinea.
Making every baby count: a facility-based audit and review of stillbirths and neonatal deaths in The Gambia
Dr Okomo won a pump priming grant to do an audit and review of stillbirths and neonatal deaths in a number of sites in The Gambia. The study will take place at government health centres in the Western Region Division, in collaboration with the Ministry of Health and UNICEF. The data will be collected at the labour wards of six major health centres that provide obstetric care in the region. The resulting report will detail the annually births and the total of stillbirths and neonatal death per facility per year in order to better understand the issues relating to maternal and neonatal mortality and prepare for more substantial funding to address them.
Maternal IgG and Neonatal Innate Immune Cells
This study will examine how maternal antibodies activate innate immune cells in the newborn using flow cytometric methods and cell culture techniques. This subject is important to investigate in the context of naturally occurring antibody but also antibody induced by vaccines given to pregnant women. Several mechanisms could influence neonatal immune responses to vaccination and infection, such as direct interaction of the antibody with the neonatal Fc receptors or mechanisms that can induce “trained immunity”. For his study, Dr. Darboe will be collecting and stimulating cord blood samples from babies whose mothers have been vaccinated in pregnancy with TLR ligands and control antigens.
Periscope: Developing improved vaccines against pertussis
This comprehensive multi-partner project aims to better understand immunity to pertussis in order to improve current acellular pertussis vaccines, which appear to offer imperfect protection. We are leading the multi-site clinical trials recruiting infants and pregnant women with one arm being conducted at the MRC Unit The Gambia- the only site in Africa-, 3 others in the UK, Holland and Finland. The aim of these trials is to evaluate the impact of maternal immunisation on responses to whole cell or acellular pertussis vaccination in infancy and impact on longer-term immunological memory.
Audio-visual tool to train Primary Health workers to strengthen the Expanded Program on Immunization program in The Gambia
This project is being carried out in collaboration with the EPI program in the Gambia and will develop an audio-visual tool called ‘Speaking Book’ to strengthen the understanding of EPI vaccines by caregivers and health workers and improve their communication.
The book will be recorded by local speakers in both Wollof and Mandinka and its acceptability and utility will be tested in a number of non-MRC affiliated health centres throughout the country using a mixed-methods approach.
GAIA Extension : Global Alignment of Immunization safety assessment in pregnancy
This project will assess how case definitions developed by the Brighton Collaboration and their methods of consensus development will perform in a real world field setting of a clinical trial. The GAIA project was launched to meet the WHO’s call for a global approach to active monitoring of the safety of vaccines and immunization in pregnancy, specifically for low and middle income countries (LMIC). It aims to improve the quality of outcome data from clinical and observational studies related to immunization in pregnancy especially in LMIC. Dr. Ed Clarke’ PROPEL trial will be examining the impact analysis of the GAIA outputs, having used these outputs from the start of the study and generating data to be able to assess usefulness and feasibility of various GAIA outputs in The Gambia, which is a LMIC.
TB Biomarker study
This NIH-funded collaborative project (PI: M Levin, Imperial College London) will validate previously described biosignatures for the diagnosis of TB in children in stored samples from larger cohorts including from Gambia, South Africa, Malawi using RNA and protein-signatures and bioinformatics approaches.
Reach4Kids: Improving diagnosis and management of childhood tuberculosis in the Gambia
The diagnosis of TB in children based on microbiological confirmation remains difficult due to the pauci-bacillary nature of the disease. Childhood TB is therefore underreported and underestimated nationally and internationally and preventive strategies are poorly applied. This program of work aims to evaluate performance of current diagnostics, develop new biosignature-based tools, understand household transmission and implement strategies for contact tracing for TB-exposed children that can be integrated into the community care to be delivered by the NLTP.
Reach4Kids Africa: Improving diagnosis and management of childhood tuberculosis in Africa
Built on the insights and successes of an MRC Programme Grant awarded to Prof Kampmann to improve the management of Childhood TB in The Gambia, funding has been received to extend our diagnostics studies to three additional sites in Africa: Mali, Nigeria and Tanzania. The project is working with colleagues in academic institutions and partners in the National Leprosy and Tuberculosis Programs (NLTP) at all sites to set up prospective cohorts of children with TB- Find and Treat (FaT)- and implement household contact screening at sentinel sites- Screen and Prevent (SaP).
Improving the Diagnostics of Childhood Tuberculosis in High Burden Settings
In order to establish a fast and accurate detection of TB in children a new point-of-care diagnostic test is needed. Professor Kampmann and Dr. Toyin Togun (McGill University) aim to further validate a novel cytokine-based diagnostic biosignature that was identified in unstimulated plasma supernatants from HIV-negative children in The Gambia as part of the MRC-funded program of research into childhood TB, set up by Prof Kampmann since 2012 (Reach4Kids). Secreted cytokines in supernatants harvested from whole blood assays will be measured using a multiplex bead assay.
A randomized, observer-blind, non-inferiority trial to evaluate alternative human papillomavirus (HPV) vaccination schedules in females in West Africa
This randomized trial will assess the immunogenicity of one or two doses of a 9-valent HPV vaccine in 9 to 14 year old females and will assess the safety and immunogenicity of one and two doses of the vaccine in 4 to 8 year old females. This project will provide data which could broaden the current licensure of the vaccine for those aged only 9 years and above and could facilitate school age based delivery.
Maternal Immunization with MenAfriVac®
This phase 3 trial will assess the potential role of delivering MenAfriVac®, the meningococcal serogroup A conjugate vaccine manufactured by the Serum Institute of India Pvt. Ltd, to expectant mothers to protect their infants. As tetanus toxoid is the conjugated protein, the vaccine could replace one of the routine antenatal doses. MenAfriVac® is currently recommended for infants routinely from 9 months upward. Vaccinating expectant mothers could close the window of susceptibility up to this age.
The microbiome, antibiotics and vaccine immunogenicity
This sub-study will be part of the MenAfriVac trial. It will provide an opportunity to monitor the development of the intestinal microbiome from birth to 10 months of age and to assess the effects that any antibiotics, administered in early life for clinical indication, have on this development. Furthermore, to study the downstream effects of distinct microbial profiles on baseline and post-vaccination transcriptomic and metabolomic profiles and immune cell phenotypes, and on the serological responses to vaccination.
A pragmatic trial to quantitatively and qualitatively assess different techniques for the administration of fractional dose of inactivated polio vaccine (IPV)
Acute shortages of IPV, reflecting unpredicted limitations to manufacturing capacity, have resulted in the WHO recommending that ‘fractional’ (1/5th 0.1mL) doses of the vaccine, administered by the intradermal route. These fractional intradermal doses will need to be delivered in emergency community campaigns. This trial specifically assesses the practicality of delivering such large scale intradermal campaigns in a rural setting in West Africa and is expected to provide key data required by the GPEI and WHO.
A randomized, controlled, double-blind, phase 3 trial to evaluate the effects of maternal or neonatal pneumococcal conjugate vaccination on pneumococcal
This trial aims to examine novel ways to prevent pneumococcal disease in early infancy. We are evaluating the impact of vaccinating either expectant mothers in the third trimester of pregnancy or newborn infants in the first week of life on vaccine-type pneumococcal carriage in the nasopharynx, compared with the usual EPI schedule in a randomised controlled clinical trial enrolling 600 mothers and their infants. The effects of the alternative schedules on serological responses, memory B-cells, carrier-protein specific T-cells in the infant and pneumococcus-specific responses in breast milk are also being examined as exploratory the endpoints.
TB Sequel: Research networks for health innovation in sub-Saharan Africa
A substantial proportion of microbiologically cured TB patients are left with some level of impairment of pulmonary function. Understanding which factors lead to more extensive disease and the pathophysiological basis for this is important. TB-sequel is a multi-site prospective clinical study, enrolling around 1600 patients with newly diagnosed TB in Gambia, Tanzania, South Africa and Mozambique. It aims to determine factors that predict long-term lung sequelae in order to provide avenues for early implementation of new therapeutics. Additionally, we are measuring the socio-economic impact of TB to better understand costs to families associated with TB.
The aim of this project is to develop a point of care test for diagnosis of active TB based on the measurement of a combination of 7 markers in plasma using a multi-plex lateral flow test. The overall objective of the study is to incorporate the six-marker signature into a multiplex UCP-LFA format, referred to as TransDot, for finger-prick blood testing.
MRC at LSHTM is involved in the discovery of new TB biomarker candidates using innovative approaches. Using samples collected through the TB case-contact (TBCC) platform at MRC at LSHTM, we aim to define biosignatures of protection to Mtb infection using ‘omics analysis of samples from highly TB exposed but persistently TST negative (uninfected) subjects. Analysis of RNA, plasma (metabolites and antibodies) together with Flow cytometry will allow profiling of the ‘global space’ in TB.
GC6-2013: Biomarkers for TB consortium
This project aims to identify and validate signatures of risk of TB disease. Household contacts at 4 African sites household were followed for 2 years. Blood samples were collected at enrolment, and after 6 and 18 months of follow-up. Persons with lung TB were identified during follow up. Samples from the TB cases were analysed and from matched controls, to identify prospective correlates of risk of TB disease.
A phase 3, randomized, double-blind study to evaluate the safety, tolerability, lot-to-lot consistency, immunogenicity, and non-interference with concomitant vaccinations
This phase 3 trial of a novel pneumococcal conjugated vaccine follows directly on the back of a phase 1/2 trial of the same vaccine we have recently successfully completed at the Unit. The trial is recruiting 2250 infants aims to generate the safety and immunogenicity data required to support future licensure and WHO pre-qualification of the vaccine so it can later be made available through GAVI/UNICEF and other supply routes.
VAC058 - A Phase I trial to assess the safety and immunogenicity of ChAd63 ME-TRAP - MVA ME-TRAP heterologous prime-boost vaccination co-administered with EPI vaccines in Gambian infants – in collaboration with the Malaria Vectored Vaccines Consortium 2 (MVVC2), the Jenner Institute in Oxford, UK and the Université Cheikh Anta Diop de Dakar (UCAD), Senegal
Despite a decline in transmission in some parts of Africa, malaria remains a major public health concern, making the development of an effective vaccine still of high priority. Heterologous prime-boost vectored vaccination, using Chimpanzee Adenovirus 63 (ChAd63) and Modified Vaccinia virus Ankara (MVA) encoding ME-TRAP (thrombospondin-related adhesion protein fused to a multiepitope string), induces a strong T cell response, playing a key role in protection. Previous trials in Gambian, Senegalese, Kenyan and Burkinabe adults and children have shown the vaccine to be safe and highly immunogenic, with substantial efficacy observed in adults. This trial aims to extend the assessment of safety and immunogenicity of this vaccination strategy to a sample of African infants and neonates, representing the target age group for malaria vaccination. As, if licensed, this vaccine will be given to infants who receive childhood immunizations, serology will be performed to confirm all infants achieved protective titres to routine Expanded Programme Immunization (EPI) vaccines.
Acute respiratory infections are a major cause of morbidity and mortality worldwide. No formal surveillance system exists in The Gambia to assess the proportion of influenza-like illness (ILI) in children <5 years of age caused by influenza, RSV and other respiratory viruses. CSDILI is a 1-year prospective, observational study of the prevalence and seasonality of respiratory viral infections in children <5 years old presenting to the MRC Clinical Services Department. This information will help inform future vaccine strategies for influenza and RSV. Other secondary outcomes will include assessment of inappropriate antibiotic use for ILI and how this can be improved.
Exploring the relationship between nutrition and vaccine responses
This study seeks to relate anthropometric, metabolic and proteomic data to vaccine response with a view to better understanding the role of nutritional parameters on vaccine responses. The responses will be linked to a wide range of antigens given around the vulnerable ages and around the age of growth faltering.
Seroepidemiology study of Zika virus and other arboviral fevers in selected West African countries
Continuous disease surveillance at a global level is required as arboviruses cause large outbreaks and epidemics with high disease burden in the affected population. This study is a seroepidemiological survey should conducted to define the dynamics of the infection and disease, implement preventive programs and stimulate the interest for the development of specific drugs and vaccines.