Student Awarded

Mohau Steven Makatsa

Mohau Steven Makatsa

Country: South Africa

Project Title: Characterization of Mtb-specific Th22 cells

Institution: University of Cape Town

I will visit the laboratory of Dr. Mario Roederer, Vaccine Research Center, NIAID/NIH, USA and measure IL-22 responses in BCG-vaccinated rhesus macaques to investigate IL-22 responses after vaccination. Dr. Roederer and his collaborators have been testing the existing TB vaccine (BCG) and new TB vaccines in a non-human primate model of stringent TB challenge. Recently they have found that certain immunization routes (aerosol and intravenous) induce a greater magnitude of CD4+ and CD8+ T cell responses than conventional intradermal vaccination, as well as far superior protection from infection using a stringent Mycobacterium tuberculosis challenge. They currently only measure Th1 CD4+ immunity and have not investigated IL-22 responses. I will establish whole blood assays to measure IL-22 in rhesus macaques vaccinated with BCG via different routes. Investigating IL-22 responses in an NHP model of vaccination and protection from infection may lead to important insights into the significance and role of these cells in protective immunity to TB. This will extend my studies on human TB samples, which are largely descriptive.

Report Back – Skills Gained

Visit to Dr Mario Roederer’s lab, Vaccine Research Center, NIAID/NIH, USA

Courses attended: Advanced Flow Cytometry workshop

  • standardizing flow cytometry instrument (Calibration, Performance and Monitoring Standards)
  • 28 color flow cytometry panel development
  • Flow Data Analysis – Data Validation (FlowJo software) and Exploratory tools (FlowAI, FlowSOME, tSNE, UMAP, COMPASS etc.)
  • Flow cell sorting

Laboratory work:

  • Optimized flow panel to investigate cytokine production by different lymphocytes subsets
  • Perform whole blood assay on BCG vaccinated macaques
  • Run optimized flow panel on BCG vaccinated macaques

African Supervisor

Wendy Burgers

Wendy Burgers

African Host Country: South Africa

Institution: University of Cape Town

Laboratory: HIV/TB Immunology and Pathogenesis Group at the IDM

I have been working in the HIV immunology field for 15 years, beginning with applied HIV vaccine research, and then focusing on basic research to understand HIV immunity and pathogenesis, and how HIV affects immunity to major co-infections in our setting, such as TB. In my laboratory, we investigate how HIV affects the immune response to Mycobacterium tuberculosis in HIV-TB co-infected individuals, both in blood and at the site of disease, the lungs, with a focus on adaptive immunity. We also study the immunology of HIV pathogenesis, seeking to understand how immune hyperactivation results in ineffective immunity and drives progression to disease. Current work focuses on characterizing an understudied CD4+ T helper subset, Th22 cells, which may be important in protective immunity to TB.

The work in the laboratory is funded by the Wellcome Trust, the NIH and the European and Developing Countries Clinical Trials Platform (EDCTP), with additional local funding from the SA Medical Research Council, National Research Foundation and the PRF.

International Supervisor

Mario Roederer

International Host Country: United States of America

Institution: National Institute of Health

Laboratory: ImmunoTechnology Section at Vaccine Research Center

A primary focus of my laboratory includes defining mechanisms of vaccine-mediated protection. An important focus in HIV and TB research is on mucosal responses at the portal of infection. We developed and characterized a vectored vaccine delivery platform aimed at generating T cell responses in the lung to protect against TB. This has led now to multiple complex TB challenge experiments, both completed and ongoing, to assess whether the large T cell responses we generate are efficacious. I have also been heavily involved in creating and optimizing assays and flow cytometry technology for application to immunology. This has been a broad-based effort in software and analytical tools, chemistry for new probes, hardware, and assays. The efforts in my laboratory have fundamentally changed how flow cytometry is used to assess immune function. In the past few years, we have integrated cytometry-based proteomics with single-cell transcriptomics to provide an unprecedented view of the functions and interactions of leukocytes. I have over 350 publications, >47 000 citations and an H-index of 112.