Development and Evaluation of a Cryopreserved Whole-Parasite Vaccine in a Rodent Model of Blood-Stage Malaria

Infection with malaria parasites continues to be a major global public health issue. While current control measures have enabled a significant decrease in morbidity and mortality over the last 20 years, additional tools will be required if we are to progress toward malaria parasite eradication. Mala...

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Published in:	mBio 2021-10, Vol.12 (5), p.e0265721-e0265721
Main Authors:	Stanisic, Danielle I, Ho, Mei-Fong, Nevagi, Reshma, Cooper, Emily, Walton, Maddison, Islam, Md Tanjir, Hussein, Waleed M, Skwarczynski, Mariusz, Toth, Istvan, Good, Michael F
Format:	Article
Language:	eng
Subjects:	Animals Antibodies, Protozoan - blood Antibodies, Protozoan - immunology Antigens, Protozoan - immunology Erythrocytes - parasitology Female Immunity, Cellular Immunogenicity, Vaccine Liposomes - administration & dosage Malaria - immunology Malaria - prevention & control Malaria Vaccines - administration & dosage Malaria Vaccines - immunology Malaria Vaccines - standards Mice Mice, Inbred BALB C Mice, Inbred C57BL Plasmodium yoelii - immunology Research Article T-Lymphocytes - immunology Vaccines
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Summary:	Infection with malaria parasites continues to be a major global public health issue. While current control measures have enabled a significant decrease in morbidity and mortality over the last 20 years, additional tools will be required if we are to progress toward malaria parasite eradication. Malaria vaccine research has focused on the development of subunit vaccines; however, more recently, interest in whole-parasite vaccines has reignited. Whole-parasite vaccines enable the presentation of a broad repertoire of antigens to the immune system, which limits the impact of antigenic polymorphism and genetic restriction of the immune response. We previously reported that whole-parasite vaccines can be prepared using chemically attenuated parasites within intact red blood cells or using killed parasites in liposomes, although liposomes were less immunogenic than attenuated parasites. If they could be frozen or freeze-dried and be made more immunogenic, liposomal vaccines would be ideal for vaccine deployment in areas where malaria is endemic. Here, we develop and evaluate a Plasmodium yoelii liposomal vaccine with enhanced immunogenicity and efficacy due to incorporation of TLR4 agonist, 3D(6-acyl) PHAD, and mannose to target the liposome to antigen-presenting cells. Following vaccination, mice were protected, and strong cellular immune responses were induced, characterized by parasite-specific splenocyte proliferation and a mixed Th1/Th2/Th17 cytokine response. Parasite-specific antibodies were induced, predominantly of the IgG1 subclass. CD4 T cells and gamma interferon were critical components of the protective immune response. This study represents an important development toward evaluation of this whole-parasite blood-stage vaccine in a phase I clinical trial. Malaria is a mosquito-borne infectious disease that is caused by parasites of the genus, . There are seven different spp. that can cause malaria in humans, with P. falciparum causing the majority of the morbidity and mortality. Malaria parasites are endemic in 87 countries and continue to result in >200 million cases of malaria and >400,000 deaths/year, mostly children
ISSN:	2150-7511 2150-7511