DECIPHER
MPOX
Deciphering host genetics and viral determinants of mpox epidemiology in the Democratic Republic of Congo
Background
Monkeypox virus (MPXV) is a member of the Poxviridae family that includes equatorial Africa following casual human to animal or human to human transmission , recent events have seen an increased incidence with indications of sexual transmission. The disease is characterized by fever, muscle aches, skin rash, lymphadenopathy, oral sores, sore throat, cough, etc. Within any cluster of high risk contacts of a case mpox; however, not everyone exposed develops clinical disease. Moreover, among those contacts who develop mpox, not everyone gets severe disease or dies.
Hypothesis
Host genetic & viral factors explain the differential outcomes following exposure to MPXV.
Objectives
To determine the host genetic and viral determinants of mpox disease in Kamituga area, South Kivu province, DRC. Specifically, we will:
(I) establish well phenotyped cohorts of house-hold contacts;
(II) determine rare variants via family trios;
(III) undertake RNASeq for transcriptomics;
(IV) study differential cellular immunity profiles using digital cell sorting (DCS), and
(V) identify viral variants that drive severe disease.
Methods
Whole exome sequencing (WES), transcriptomics and DCS studies of house-family contacts clinically prequalified by PCR and serological testing. Virus gDNA will be reverse transcribed from sequenced host RNA and characterized by comparative genomics and phylogeny.
Potential Impact
This project will elucidate host genetic & viral determinants of susceptibility to mpox disease in context of natural exposure and infection; that may serve as correlates of immune protection following vaccination.
National Institue for Communicable Diseases
It is a national public health institute for South Africa, providing disease surveillance, specialized diagnostic services, outbreak response, public health research and capacity building to support the government’s response to communicable disease threats. It has a sequencing core facility that conducts next- generation sequencing for diagnosis and outbreak support.
The NICD has several laboratories that are World Health Organization (WHO) collaborating partners, providing reference diagnostic services and surveillance for communicable diseases. The study will utilize some of these laboratories for the laboratory assays.
Makerere University
The Makerere University will lead the scientific aspects of the study through the Center for Equitable Global Health Initiatives based at Makerere University Lung Institute (MLI/CEGHI).
The MLI/CEGHI has championed health research that incorporates clinical care and training. They have experience and expertise in conducting pandemic responsive research thanks to the many research projects conducted during the COVID-19, Ebola outbreak (2022) and more recently the mpox vaccine trial in DRC where they are supporting CUB to conduct the smart trial.
The MLI/CEGHI has scientists that are leaders in global health research and programming in Uganda and the region for over 2 decades. The MLI/CEGHI has been involved in research projects that span biomedical, vaccinology, therapeutic and public health spheres. They are leading a trial that will evaluate the safety and immunogenicity of Ebola vaccines in Uganda.
Further, MLI/CEGHI is acting as a sponsor for the SMART trial’: —a cluster randomized ring vaccination trial of a smallpox vaccine (MV-BN) among household contacts of mpox cases in DRC. The MLI/CEGHI is located within the Makerere University College of Health Sciences and has a long-standing collaboration with the Makerere University Biomedical Research Centre (MakBRC) situated with the Makerere University College of Health Sciences which provides laboratory services. The laboratories include BSL-3 Mycobacteriology Laboratory, a CAPA accredited Immunology Laboratory and a state-of-the-art Molecular laboratory. MLI/CEGHI has experience in cohort studies and some of the cohorts established include for conditions such as Ebola, COVID-19, Ebola, Asthma, COPD among others.
Catholic University of Bukavu
The Catholic University of Bukavu (CUB) Democratic Republic of Congo: is located in the eastern Democratic Republic of Congo (DRC) in Bukavu, the capital city of South Kivu province (bordering Rwanda and Burundi). The CUB comprises a multidisciplinary team including clinicians, laboratory scientists/ microbiologists, pharmacologist, public health and clinical epidemiologists and social scientists with experience conducting population- and hospital based research in the DRC with the aim of strengthening the health system in a post conflict area. The team has also a long-term experience with network collaboration (John Hopkins university/cholera vaccine clinical trial, 5 year German Federal Ministry of Education and Research project/Sepsis) and recently finalised a 10-year collaboration with Flemish universities grant programmes.
CUB contributes a pre-existing platform for clinical research, a network of stakeholders, experience with public/community engagement, access to national health databases, experienced mentorship, and hands-on training on long-term epidemic prone diseases in the region. The CUB via the CTDGH brings transdisciplinary and data driven approaches for knowledge translation to specifically contribute to different work packages.
CUB will partner with the national laboratory of biomedical science in the DRC that has a satellite site at the CTDGH to leverage on the long-term experience on disease outbreaks. Similarly, CUB will closely work with the centre for natural science of Lwiro, the largest of its kind in the region and with a very large network of experienced scientists working on various One Health topics as seen in the tropical region.
Uganda National Health Research Organisation
The Uganda National Health Research Organisation (UNHRO) overseas state-of-the-art laboratories located at key implementing institutions, including the Uganda Virus Research Institute (UVRI), Joint Clinical Research Center (JCRC), and the Medical Research Council/London School of Hygiene and Tropical Medicine (MRC/LSHTM) Unit at UVRI. These facilities feature BSL-3 laboratories, flow cytometry, and sequencing capabilities, supported by cutting-edge infrastructure and highly skilled personnel.
Among other end-point assays that support on-going clinical and biomedical research, the laboratories also specialize in virus cultures such as HIV, SARS-CoV-2, MPXV, Measles, and Adenovirus, as well as cytokine profiling and transcriptomics. They are GCLP-compliant and hold international accreditations from organizations such as the American College of Pathology, SANAS, Africa CDC, and the World Health Organization, among others.
UNHRO laboratories possess extensive expertise in virology and molecular biology, including the evaluation of innate and vaccine-induced immune responses. They have supported research on experimental HIV vaccines, the Ebola Zaire vaccine, the Rift Valley Fever vaccine, and the development of the first self-amplifying SARS-CoV-2 mRNA vaccine (samRNA/LNP).
Uganda Virus Research Institute
The institute possesses a BSL-3 laboratory which is a state-of-the-art laboratory with expertise in virus cultures such as HIV, SARS-COV-2, MPXV and Adenovirus. UVRI is also the CEPI-centralized laboratory for Ebola and Marburg. The laboratories are GCLP accredited. The laboratory has expertise in evaluating vaccine-induced responses including experimental HIV vaccines, experimental Ebola Zaire Vaccine, experimental Rift Valley Fever vaccines, and the first self-amplifying SARS COV-2 mRNA vaccine (samRNA/LNP).
McMaster University
It is a global leader in health education, research and training. It has state–of–the-art laboratories and has been involved in groundbreaking research globally. The University brings to the study an innovative network of researchers that have undertaken research that has led the way in shaping health care and patient treatment around the globe. Currently, the University is supporting the SMART trial in DRC that is evaluating the ability of a vaccine to prevent infection among contacts of mpox.
National Institute for Biomedical Research
The National Institute for Biomedical Research (INRB) serves as the National Biomedical Research Laboratory for the Ministry of Health of the Democratic Republic of Congo (DRC) and was established in 1975. It is a collaborating center of the World Health Organization (WHO). Its departments have the mission of carrying out medical and biological analyses, applied and translational research, monitoring communicable diseases and promoting professional growth and development. It is a multidisciplinary institute that collectively has decades of experience in both the identification, treatment, and prevention of diseases in the DRC. Its foundations are the performance of medical and biological analyses, applied and translational research, surveillance of communicable diseases and the promotion of professional growth and development. INRB has continually developed and trained quality researchers and produced outstanding results, most recently concrete efforts in control, prevention, and research in the recent epidemics.
University of Liverpool
The University of Liverpool has an international reputation in the field of infectious diseases, is one of the largest centres in the UK for infectious disease research and hosts the Centre for Global Vaccine Research and the Pandemic Institute. The University has several high containment laboratories for both human and animal pathogens including Containment Level 3 (Biosafety Level 3). The Respiratory and Emerging Viruses Group, led by Professor Julian Hiscox has extensive experience in the use of high throughput approaches to study biological and chemical threats.
The lab works closely with UK and international partners to aid in diagnostic efforts and contributed to the European Mobile Laboratory that deployed to Guinea during the West African Ebola crisis. Researchers from the group supported the Liverpool COVID-19 response as part of ISARIC-4C and COG-UK, providing clinical sample characterisation using high throughput Illumina and Oxford Nanopore sequencing platforms. Laboratory work is integrated with bioinformatic and machine learning approaches, which have been used to identify markers of survival in Ebola infections and predict the evolution of COVID-19 and related respiratory viruses.
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Participating Institutions
