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Updated: Jul 6, 2025
High Yield Purification of Plasmodium falciparum Merozoites For Use in Opsonizing Antibody Assays
Published on: July 17, 2014
A candidate antibody drug for prevention of malaria
Katherine L Williams1, Steve Guerrero2, Yevel Flores-Garcia3
1Atreca, Inc., San Carlos, CA, USA. kwilliams@atreca.com.
Insights
New monoclonal antibodies offer improved malaria protection for young children. Researchers identified promising antibody candidates to complement existing vaccines, aiming for low-cost, scalable production for global pediatric use against malaria.
Area of Science:
- Immunology and Infectious Diseases
- Vaccinology and Antibody Therapeutics
Background:
- Malaria causes a high mortality rate in children under 5, with current vaccines showing modest efficacy.
- Complementary strategies, such as monoclonal antibodies, are crucial for malaria eradication efforts.
- The RTS,S/AS01 (Mosquirix) vaccine targets the Plasmodium falciparum circumsporozoite protein.
Purpose of the Study:
- To characterize B cell repertoires in RTS,S/AS01 vaccinees.
- To discover and develop novel monoclonal antibodies as potential malaria therapeutics.
- To identify antibodies suitable for low-cost, scalable manufacturing for pediatric populations.
Main Methods:
- Sequencing of over 28,000 antibody variable domains from 45 RTS,S/AS01 vaccinees.
- In vitro binding assays and in vivo antimalaria activity testing in mouse models.
- Biomanufacturing assessments and protein stability assays for antibody optimization.
Main Results:
- Identified correlations between Plasmodium falciparum circumsporozoite protein responses and antibody efficacy.
- Discovered and selected two lead monoclonal antibodies, AB-000224 and AB-007088, for further development.
- Engineered an optimal clone (MAM01) with favorable manufacturing and drug properties for clinical advancement.
Conclusions:
- Monoclonal antibodies can be developed to enhance malaria protection, particularly for vulnerable pediatric populations.
- The identified antibodies and engineered clone MAM01 show promise as scalable, cost-effective malaria therapeutics.
- Further clinical development of MAM01 aligns with WHO guidelines for global distribution and malaria control.
Abstract:
Over 75% of malaria-attributable deaths occur in children under the age of 5 years. However, the first malaria vaccine recommended by the World Health Organization (WHO) for pediatric use, RTS,S/AS01 (Mosquirix), has modest efficacy. Complementary strategies, including monoclonal antibodies, will be important in efforts to eradicate malaria. Here we characterize the circulating B cell repertoires of 45 RTS,S/AS01 vaccinees and discover monoclonal antibodies for development as potential therapeutics. We generated >28,000 antibody sequences and tested 481 antibodies for binding activity and 125 antibodies for antimalaria activity in vivo. Through these analyses we identified correlations suggesting that sequences in Plasmodium falciparum circumsporozoite protein, the target antigen in RTS,S/AS01, may induce immunodominant antibody responses that limit more protective, but subdominant, responses. Using binding studies, mouse malaria models, biomanufacturing assessments and protein stability assays, we selected AB-000224 and AB-007088 for advancement as a clinical lead and backup. We engineered the variable domains (Fv) of both antibodies to enable low-cost manufacturing at scale for distribution to pediatric populations, in alignment with WHO's preferred product guidelines. The engineered clone with the optimal manufacturing and drug property profile, MAM01, was advanced into clinical development.
