Cross-species Malaria Immunity Induced by Chemically Attenuated Parasites

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2013 Jul 19

PMID 23863622

Citations 34

Authors

Michael F Good

Jennifer M Reiman

I Bibiana Rodriguez

Koichi Ito

Stephanie K Yanow

Ibrahim M El-Deeb

Michael R Batzloff

Danielle I Stanisic

Christian Engwerda

Terry Spithill

Stephen L Hoffman

Moses Lee

Virginia McPhun

Affiliations

Soon will be listed here.

Abstract

Vaccine development for the blood stages of malaria has focused on the induction of antibodies to parasite surface antigens, most of which are highly polymorphic. An alternate strategy has evolved from observations that low-density infections can induce antibody-independent immunity to different strains. To test this strategy, we treated parasitized red blood cells from the rodent parasite Plasmodium chabaudi with seco-cyclopropyl pyrrolo indole analogs. These drugs irreversibly alkylate parasite DNA, blocking their ability to replicate. After administration in mice, DNA from the vaccine could be detected in the blood for over 110 days and a single vaccination induced profound immunity to different malaria parasite species. Immunity was mediated by CD4+ T cells and was dependent on the red blood cell membrane remaining intact. The human parasite, Plasmodium falciparum, could also be attenuated by treatment with seco-cyclopropyl pyrrolo indole analogs. These data demonstrate that vaccination with chemically attenuated parasites induces protective immunity and provide a compelling rationale for testing a blood-stage parasite-based vaccine targeting human Plasmodium species.

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