Poster Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2023

Age-dependent differences in the composition of malaria antigen-specific CD4 T cells (#175)

Mayimuna Nalubega 1 2 , Dean Andrew 1 , Megan Soon 1 , Nicholas Dooley 1 , Jessica Loughland 1 , Nankya Felistas 3 , Kenneth Musinguzi 3 , John Rek 3 , Isaac Ssewanyana 3 , Emmanuel Arinaitwe 3 , Moses Kamya 3 , Prasanna Jaganathan 4 , Margaret Feeney 5 , Michelle Boyle 1 6
  1. QIMR Berghofer, Brisbane, Queensland, Australia
  2. The University of Queenland, Brisbane, Queensland, Australia
  3. Infectious Diseases Research Collaboration, Kampala, Uganda
  4. Stanford University, Stanford, California, USA
  5. University of California san Francisco, San Francisco, California, USA
  6. Cellular Responses to Disease and Vaccination, Burnet Institute, Melbourne, Victoria, Australia

CD4 T cells play a central role in the immune response to malaria. They provide signals required for parasite clearance,  antibody production and promote the development of memory cells. Age and transmission intensity have been shown to modulate  CD4 T cell function during malaria. However, the mechanisms that drive these changes are not well understood. Here we used high dimensional spectral flow cytometry and single-cell RNA sequencing to comprehensively profile parasite-specific  CD4 T cells in children and adults living in a high malaria transmission setting. Parasite-specific CD4 T cells were identified using the activation-induced markers following stimulation of PBMCs with Plasmodium falciparum-infected red blood cells. Using flow cytometry, we demonstrated that adults had higher frequencies of parasite-specific cells across multiple CD4 T cells than children. Within the parasite-specific CD4 T cell compartment,  the frequency of Th2 cells was higher in adults than children. In the single-cell RNA sequencing, we assessed four longitudinal samples per child in 3 children.  Crossectional samples from 3 adults were included for comparison. Similarly,  single-cell RNA sequencing revealed multiple transcriptionally distinct CD4 T  cell subsets in children and adults. We will compare the transcriptional profiles of parasite-specific CD4 T cells in children and adults. We will also assess the clonal changes in parasite-specific CD4 T cells over time in children. This study will provide insights into the different CD4 T cell components required for long-term protection and consequently provide targets for improved vaccine outcomes.