Evaluation of antimalarial antibodies elicited by CSP-based vaccines in humanized immunoglobulin mice 3560

Abstract Description Malaria is one of the most severe public health problems worldwide, affecting 249 million people and causing 608 thousand deaths in 2022. To date, two malaria vaccines have been approved by the World Health Organization. However, antibody (Ab)-mediated protection is short-lived and developing a vaccine that elicits durable protection remains challenging. We hypothesized that malaria vaccines that display a broader range of epitopes in a multivalent manner may elicit protective Abs with wider protective breadth. To more closely reflect how the human B cell repertoire may respond to these novel vaccines, we immunized a humanized immunoglobulin mouse model. We first analyzed the B cell receptor (BCR) sequences from harvested splenocytes to evaluate the immune response. Next, we expressed downselected BCR sequences as humanized monoclonal Abs (mAbs) and identified the epitopes they bind. Finally, we tested the protective efficacy of passively transferred mAbs in an in vivo liver malaria burden assay. Our results identified novel mAbs that provide protection comparable to CIS43LS, a leading clinical candidate that has demonstrated high efficacy in an endemic setting. These findings suggest that incorporating multiple epitopes in a vaccine can elicit Abs that bind subdominant epitopes and neutralize the parasite. Our insights can be leveraged to inform the design and development of prophylactic malaria antibodies and vaccines. Funding Sources This work was supported by the Bill and Melinda Gates Foundation (INV-009411 and INV-043758); the intramural research program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health; this material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. 2141064. Topic Categories Vaccines and Immunotherapy (VAC)