The viral pathogens theme | Research themes

VIRAL PATHOGENS THEME

Led by Professor Pontiano Kaleebu

Historically, the Unit was established to tackle the emerging HIV epidemic, and HIV research has been a long-standing strength of the Unit. In later years, the Unit expanded to address other emerging and re-emerging infections especially viruses and non-communicable diseases. This experience enabled the Unit to engage rapidly to support of SARS-CoV-2 research. Furthermore, the Unit is closely affiliated to the UVRI which is one of the few institutes in Africa dedicated to virus research. The Viral Pathogens Theme has three focus areas: viral pathogen epidemiology and interventions (VPEI); viral pathogen discovery, diversity and impact on epidemic and disease outcome (VPDD); and oncogenic virus immunovirology (OVI).

Virology research at the Unit seeks to understand the epidemiology of HIV, oncogenic and emerging/re-emerging infections and associated co-infections, to contribute to the interventions, discovery of viruses of public health importance and to understand how pathogen diversity affects epidemics and disease outcome, with the aim of facilitating the development of effective preventive and treatment therapies.

The activities are primarily hosted in the Unit’s field stations, with on-site immunology and virology, P2 and P3 laboratories and clinical research facilities. The immunology, sequencing, clinical research, General Population Cohort and Clinical Diagnostic Laboratory platforms are all key to this Theme. The high-performance cluster UMIC is also of extreme importance. The work under this Theme is closely linked with our Vaccines and Non-communicable diseases research thematic areas to allow for a healthy research intersection and exchange of relevant knowledge.

Our strong partnership with the Uganda Ministry of Health and close affiliation to the Uganda Virus Research Institute, one of the few institutes in Africa dedicated to virus research, positions us favorably to ensure that knowledge emerging from our work informs the development of useful and relevant policy and practice.

Our research focus areas are highlighted below.

Viral pathogen epidemiology and interventions (VPEI):

Building and expanding on past discoveries, our collaborative studies primarily seek to: inform interventions for HIV prevention and treatment by quantifying the magnitude and trends of infection and mortality in general and key populations; develop new interventions for HIV prevention and treatment, expanding coverage of existing tools and improving long-term health of persons living with HIV; inform the future development of targeted intervention strategies to decrease transmission and pathogenicity of Kaposi’s sarcoma associated herpesvirus (KSHV) and other oncogenic infections, by identifying environmental correlates of viral control. We also have a number of ongoing SARS-CoV-2 studies and smaller studies of other viruses.

Projects

A Phase IIb three-arm, two-stage HIV prophylactic vaccine trial with a second randomisation to compare TAF/FTC to TDF/FTC as pre-exposure prophylaxis. (PrEPVacc)
Development of an HIV negative registration cohort for future participation in an HIV vaccine study (PrEPVacc registration cohort) -
Implementation of Point of Care HIV Viral Load Monitoring to improve Viral Load Suppression among Children and Youth Living with HIV in East Africa “EAST AFRICA POINT OF CARE VIRAL LOAD STUDY” (EAPoC-VL)
A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients with COVID-19. (TICO)
An International Multicenter, Randomized, Double-Blind, Placebo Controlled Trial of the Safety and Efficacy of Anti-Coronavirus Hyperimmune Intravenous Immunoglobulin for the Treatment of Adult Outpatients in Early Stages of COVID-19 (OTAC)
Single dose liposomal amphotericin for asymptomatic cryptococcal antigenemia (ACACIA)
Efficacy, Safety, and Effectiveness of Injectable Cabotegravir /Rilpivirine in Improving HIV-1 Control in Sub-Saharan Africa: A Pragmatic Phase 3b Open-Label Randomized Controlled Trial (IMPALA Study)
A Phase Ib trial to evaluate the safety and immunogenicity of R21/Matrix-M^TM in African children living with HIV (Vac092)
A behavioural science research to determine factors that facilitate future uptake of HIV prevention products and Multi-purpose Prevention Technologies to prevent HIV and unwanted pregnancy in Sub-Saharan Africa (UPTAKE)
Sample Collection for the Development and Evaluation of Rapid Tests for Chlamydia trachomatis and Neisseria gonorrhoeae in African Countries (ABBOTT CT/NG STUDY).
Implementing oral (on-demand and daily) and long-acting Pre-exposure prophylaxis in mobile men in Sub-Saharan Africa: protocol for a type 1a implementation and effectiveness trial (MOBILE MEN)
Improving HIV Prevention among Adolescent Girls and Young Women in Uganda (EACCR3/ PeerPrEP)
Pharmackinetics and tolerability of Adjunctive Linezolid for the Treatment of tuberculous meningitis (ALTER): a Phase II trial, open-label, randomized trial
An open-label, roll-over study with rilpivirine in combination with a background regimen containing other antiretrovirals (ARVs) in human immunodeficiency virus type 1 (HIV-1) infected subjects who participated in rilpivirine pediatric studies. (ROLL OVER STUDY)
A Multicenter, Adaptive, Randomized, Controlled Trial Platform To Evaluate Safety and Efficacy of Strategies and Treatments for Hospitalized Patients with Respiratory Infections
Single Dose Liposomal Amphotericin for Asymptomatic Cryptococcal Antigenemia

Focus Area Experts

Dr. Eugene Ruzagira
Dr. Joseph Mugisha
Dr. Yunia Mayanja,
Dr. Sylvia Kusemererwa,
Dr. Joseph Lutaakome,
Dr. Freddie Kibengo,
Dr. Jonathan Kitonsa
Dr. Gloria Lubega
Dr. Ubaldo Bahemuka

Viral pathogen discovery, diversity and impact on epidemic and disease outcome (VPDD):

Using metagenomics and bioinformatic approaches, we are looking for new and re-emerging viruses of public health importance with the aim of identifying intervention tools. We study emerging HIV drug resistance patterns and predictors, notably in the era of integrase inhibitors, protease inhibitors, and PrEP, and; investigate how HIV and SARS-CoV2 diversity affect immune protection, these include characterizing recently transmitted HIV-1 viruses and their sensitivity to neutralization and profiling of SARS CoV-2 immune responses. We are also expanding our work in B cell repertoires studies and generation of monoclonal antibodies. This B cell work is to expand into other viral infections like Ebola and Rift Valley Fever.

Projects

The "Phylogenetics And Networks for Generalised Epidemics in Africa (PANGEA)" consortium
Viral Pathogen Discovery and Surveillance in Uganda
Recombination, Genetic signatures & harmonization of Oxford Nanopore in HIV-1 surveillance in Uganda and India Exploration of Virological Characteristics of recently transmitted HIV-1 viruses in Uganda and Kenya Using Next-Generation Sequencing methodologies to improve HIV-1incidence estimation
Virus surveillance to evaluate the sensitivity of both contemporary and historical HIV-1 viral strains to neutralization by broadly neutralizing antibodies to prioritise immunogens for HIV vaccine design and development.
Global Immunology and Immune Sequencing for Epidemic Response (GIISER) with aim of discovery of novel monoclonal antibodies
Comprehensive immune profiling of immune responses to COVID-19 vaccines and natural infection within the Ugandan population
CEPI Laboratory network to harmonise the assessment of vaccines against epidemic and pandemic known diseases –.
National HIV-1 drug resistance surveillance and correlates for treatment failure in Uganda (CDC and PEPFAR funded).
Relevance of minority baseline HIV-1 drug resistance mutations on treatment outcomes
COVID-19 vaccine effectiveness and variants in Uganda: a test- negative case-control study with genetic sequencing (COVVAR).
Characterizing the disease burden of Chikungunya infections through hospital-based sentinel surveillance of acute febrile illness in Uganda (Peter Piot Fellowship)
Arboviral infection study (AVI) (Peter Piot Fellowship)
Characterization of T and B cells responses in acute and early HIV-1 infection to inform HIV vaccine immunogen design
Biological predictors of treatment outcomes among Anxiety, Depression and PTSD patients in Mubende

Focus Area Experts

Dr. Jennifer Serwanga
Dr Deo Ssemwanga
Dr. Sheila Balinda
Dr. Geoffrey Kimbugwe
Dr. Nicholas Bbosa
Mr. Dan Lule
Dr. Andrew Obuku
Dr. Anne Kapaata
3. Oncogenic viruses

Our study of oncogenic viruses aims to contribute to cancer control & prevention by understanding transmission and pathogenesis in population-based studies. A cornerstone of activity relates to the Kaposi’s sarcoma virus, which is highly prevalent in the region and is the underlying cause of one of the most common cancers (KS).

Projects

Determinants of Kaposi’s sarcoma herpesvirus (KSHV) transmission in Uganda (DKT) – a longitudinal study of the determinants of KSHV shedding in saliva
Environmental determinants of KSHV transmission in rural Uganda (ENDUKU) – a longitudinal study of the impact of malaria on susceptibility to KSHV
Oral health in relation to KSHV shedding in saliva – a cross sectional study within the General Population Study
Epidemiological iNvestigatIon of Gastric Malignancies (ENIGMA) – a study of Helicobacter Pylori in rural Uganda
Evaluation of the short-term impact of vaccination against Human Papillomavirus (HPV) in rural Uganda
The Uganda Liver Disease Study (ULiDS) – an examination of the true prevalence of liver disease in rural Uganda and of progression disease related to chronic Hepatitis B (HBV) infection
Age-related clonal haematopoiesis (ARCH) in rural Uganda – prevalence and determinants
Treatment of retinoblastoma among children in Uganda – a novel approach to management with long-term follow-up of outcomes

Focus Area Expert

Professor Rob Newton
Dr Angela Nalwoga
Dr Katherine Sabourin
Dr Miriam Nakanwagi (PhD student)