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Uganda Virus Research Institute

REPUBLIC OF UGANDA

Immunology

Department of Immunology

Goal of immunology department

The overall goal is to perform cutting edge, quality research in immunology and infectious diseases in order to better predict, prevent infection, and protect from disease.

The department conducts research mostly to understand protective immune responses and pathogenesis of diseases. Its activities are largely conducted in partnership with MRC/UVRI and LSHTM Uganda Research Unit and UVRI/IAVI.

The department conducts research into the protection of the body against infection especially viral infections and protective immune responses required for the development of vaccines and diagnostics.

The department’s mandate includes undertaking studies in:

  • Studies of innate, cellular and humoral immunity,
  • Diagnostics
  • Surveillance
  • Immunomodulation including studies of disease interactions
  • Vaccine research and development

 

While there has been a strong focus on HIV there is also move to diversification including:

Investigating immunological mechanisms of survival from viral hemorrhagic fever infections; investigating correlates of protection from Rift Valley Fever infections and investigating immunological mechanisms of survival from Yellow Fever

Some examples on recent work include:

  • Establishment of VIA Internal Data Acceptance (VIA-IDA) protocol

Objective

  • To optimize and establish the Viral Inhibition Assay technology as a key functional assay for evaluating vaccine-induced functional immune responses.

Evaluation of antigen-specific T-cell responses associated with elite control of HIV replication is essential for the defining correlates of protection that should be harnessed for relevant vaccine development.

The viral inhibition assay (VIA) is a qualitative functional assay for evaluating potential anti-HIV activity for both research and clinical trial activities.

Assay reproducibility and acceptance criteria are being established so that the platform can enable data from multiple centers and multiple operators to be reported as equivalent. The assay will then be used for evaluating vaccine induced HIV-specific protective immune responses in the upcoming GREAT and PrepVacc HIV-1 vaccine trial participants

The assay will also be used for screening of our on-going longitudinal cohorts including the HIV Superinfection cohort in order to determine immune correlates of protection for the elite control of HIV in order to establish relevant determinants of protection in our population

Characteristics HIV specific antibodies that are responsible for neutralization of a broad range of HIV strains

Objective

  • To define characteristics HIV specific antibodies that are responsible for neutralization of a broad range of the locally circulating virus strains in order to inform relevant vaccine design

Researchers have found that some rare HIV infected people possess antibodies that naturalize many different strains of HIV, also called broadly neutralizing antibodies. This gives new hope to the use of antibodies as candidates for vaccine and treatment. Passive infusions of such antibodies after ART discontinuation in chronically infected patients resulted in delayed viral rebound

In natural infection, such broadly neutralizing antibodies develop in about 5-10% of the population, after several years of infection.

Uganda relying more on ART treatment to control the HIV epidemic. Challenges like drugs stock outs, ART resistance mutations, poor adherence to ART regiments, and pill burden highlight the need to find more user friendly interventions.

We will screen our HIV superinfection cohort to determine the characteristics of neutralising antibodies that dominate the locally circulating clades A, D and A/D recombinants, in order to inform what determinants to target for protection. This study will inform types of neutralising antibody-based treatments and vaccines that are relevant to our epidemic.

A Randomized, Observer-blind, Placebo-controlled, Phase 2 Study to Evaluate the Safety, Tolerability and Immunogenicity of Three Regimens of Ebola Vaccines in Healthy Adults, Including Elderly Subjects, HIV-infected Subjects, and Healthy Children in Africa

Objective

  • The primary objective is to assess safety and tolerability of the different vaccination schedules
  • Other objectives are i) to further assess antibody and cellular immune responses to different Ebola proteins and to the adenovirus and MVA backbone of the various vaccination schedules tested.
  • An Adenovirus serotype 26 (Ad26) vector expressing the glycoprotein (GP) of Ebola virus (EBOV) Mayinga variant (Ad26.ZEBOV); and the Modified Vaccinia Ankara (MVA) - Bavarian Nordic (BN) vector expressing the GPs of EBOV Sudan virus (SUDV) and Marburg virus (MARV) and the nucleoprotein (NP) of Tai Forest virus (TAFV) (MVA-BN-Filo) will be evaluated as a heterologous prime-boost regimen, in which one study vaccine is used to prime a filovirus-specific immune response and the other study vaccine is used to boost the immune response 28, 56 or 84 days later. The EBOV GP that recently circulated in West Africa has 97% homology to the EBOV GPs used in this vaccine regimen.

Major Funders

  • Janssen Pharmaceuticals (Pty) Ltd
  • Medical Research Council, UK
  • IAVI ADVANCE VISTA programme
  • National Institute of Health (NIH)
  • Wellcome Trust
  • Government of Uganda, Ministry of Finance