New Technique Helps Researchers Better Understand How Young Children Develop Immunity to Malaria

jiang malaria team2

Left to right: graduate student Chenfeng He, Professor Jenny Jiang, and graduate student Ben Wendel, the lead research team.

Researchers from the Department of Biomedical Engineering at The University of Texas at Austin are gaining a better understanding of antibody repertoire responses to malaria infection, which could improve vaccine development and design.

In a new paper in Nature Communications, researchers from Professor Jenny Jiang’s lab describe a new technique for accurately measuring antibody repertoire sequence composition. They have combined high-throughput sequencing and computational biology to create an optimized method of studying the antibody repertoire, using smaller samples of cells. This is critical for studying how the immune system behaves in infants and young children.

In this study, Jiang’s team is specifically interested in how the immune system responds before and after acute malaria infection in infants and toddlers. Infants less than 12 months old are one of the most vulnerable groups affected by malaria. However, studying this young population is challenging. Researchers are only able to work with blood draws of 4 milliliters, which are much smaller than what would be available when studying infection in adults.

In partnership with the National Institute of Allergies and Infectious Diseases, Jiang’s team is analyzing small blood samples from infants and toddlers living in Mali, both before and during acute malaria infection.

Researchers want to understand how the immune cells develop and diversify to fight malaria. In order to study the immune system from small blood draws, Jiang’s team has successfully developed an accurate technique coined: Molecular Identifier Cluster-based Immune Repertoire Sequencing (MIDCIRS). MIDCIRS can provide highly accurate and comprehensive results even when applied to as few as 1,000 B cells, which are immune cells that produce antibodies to fight infections. Researchers sequence the antibodies of these B cells, then compare the antibodies during infection to the pre-infection baseline to identify patterns associated with malaria infection.

Because of the predictable timing of malaria outbreaks, researchers are able to see how the immune system responds to a natural infection. The majority of people in these malaria-endemic regions develop infection at some point during the six-month rainy season, when mosquitos that carry the parasite are rampant.

The paper includes the major finding that the infant antibody immune repertoire is surprisingly competent at introducing mutations and diversifying in response to malaria infection. These results are relevant toward new vaccine testing.

Following the results from this study, Jiang’s team intends to further examine how the immune system diversifies and responds to malaria infection in samples from an older cohort of children.

Shared lineage example

This "antibody lineage tree" can be used to track the evolution of a clonal lineage (family of B cells that are descendants of a common ancestral B cell). Each numbered node is a unique antibody sequence; they all have similar, but slightly different sequences. The degree of similarity as well as a few biological constraints (rules that mutating antibodies are known to follow) are used to determine which nodes are connected to each other. Circled in blue is a sequence discovered in the pre-malaria blood draw, while sequences circled in pink are from the acute malaria blood draw. In this example, a pre-malaria timepoint memory B cell sequence was found to have acute malaria progeny that are further mutated and isotype-switched. The color of the node is related to the number of mututations, and the height of the node is related to the size of the unique sequence.