February 15, 2023
A novel IgG3 allotype identified in women from Papua New Guinea that modulates Fc effector functions with Professor Stephen Rogerson
Allotypes are variant forms of immunoglobulin molecules that can alter antibody functions such as engagement of complement or Fc receptors found on immune cells. In pregnant women from Papua New Guinea we identified a novel IgG3 allotype that is common in women of Sepik origin, and characterised its association with pregnancy malaria. Using variants of a monoclonal antibody including the new allotype, we examined the effects of the mutations on antibody functions.
Professor Stephen Rogerson, Head of Malaria Laboraotry, Doherty Institute and Lead Investigator, Australian Centre of Research Excellence in Malaria Elimination
Polymorphisms associated with immune escape in 34 Plasmodium falciparum vaccine antigens with Myo Naung
Pathogen populations exposed to host immunity acquire and maintain polymorphisms in surface proteins to escape immune responses, but there are many other polymorphisms that are acquired through other evolutionary processes. Defining polymorphisms that contribute to antigenic diversity can identify immune targets and help to prioritize variants for development of vaccines with broad efficacy. Here, we aimed to identify polymorphisms associated with immune escape of P. falciparum for 34 malaria antigens being investigated as vaccine candidates by measuring allelic turnover between consecutive infections in longitudinal cohorts conducted in Papua New Guinea. We sequenced the antigen genes using multiplexed long-read amplicon sequencing in 550 clinical P. falciparum isolates from 240 children. To identify immune escape polymorphisms, the turnover rate of variant alleles within host was compared to the background turnover rate in the parasite population. Positive hits at known antigenic sites such as the cluster 1 loop (c1L) of AMA1 or B- or T-cell epitopes within the C-terminal domain of CSP validate this epidemiological approach.
Myo Naung, PhD Candidate, Walter and Eliza Hall of Medical Research