Bayer Pharmaceuticals PhD Prize:
Molecular characterization of public antibodies in human malaria

Katharina Imkeller1,2, Hedda Wardemann1
 
1 Department of B cell Immunology, German Cancer Research Center, Heidelberg, Germany
2 Faculty of Biosciences, Heidelberg University, Heidelberg, Germany
 
The humoral immune response plays a major role in acquired immunity towards Plasmodium falciparum (Pf), a causative agent of human malaria. Circumsporozoite protein (CSP) is the major surface protein of the pre-erythrocytic stage of Pf and some monoclonal antibodies directed against CSP have been shown to convey protection against infection. In this work we investigate the underlying molecular features of protective anti-CSP antibodies, which were previously not understood.
 
We characterize the human B cell response to the central repeat region of CSP by sequencing paired heavy and light immunoglobulin transcripts of single B cells from malaria exposed donors. Using a pairwise alignment tool that we developed to determine the similarity of antibody responses, we identified clusters of CSP specific antibodies with an amino acid sequence similarity of over 90% shared by different individuals. We recombinantly express these antibodies, characterize their binding behavior to CSP and test their Pf inhibition. Our data provide insights into the molecular mechanism underlying the clonal selection and affinity maturation of human B cells expressing protective antibodies against CSP.

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