Live attenuated pre-erythrocytic malaria vaccines

Abstract

Although recent control measures have significantly reduced malaria cases and deaths in many endemic areas, an effective vaccine will be essential to eradicate this parasitic disease. Malaria vaccine strategies developed to date focus on different phases of the parasite's complex life cycle in the human host and mosquito vector, and include both subunit-based and whole-parasite vaccines. This review focuses on the 3 live-attenuated malaria vaccination strategies that have been tested in humans to date, and discusses their progress, challenges and the immune correlates of protection that have been identified.

Keywords: CPS, Chemoprophylaxis and Sporozoite immunization; CQ, chloroquine; CSP, circumsporozoite protein; GAP, Genetically Attenuated Parasite; ITV, Immunization-Treatment-Vaccination; Malaria; P. falciparum; PfSPZ, P. falciparum sporozoite vaccine; RAS, Radiation Attenuated Sporozoites; attenuation; i.d., intradermal; i.v., intravenous; pre-erythrocytic; s.c., subcutaneous; whole-parasite vaccines.

Figure 1.

Live attenuated pre-erythrocytic malaria vaccines tested in human volunteers. (A) In the PfSPZ strategy, parasites are irradiated while in the mosquito vector, and arrest at different times during early development (red arrows) depending on the specific mutations induced. Late liver stages are absent, and no merozoites are released (indicated in the figure by the fact that those stages are greyed out). (B) In CPS under chloroquine (CQ) coverage, parasites complete liver stage development, and erythrocyte-infective merozoites are released, but the presence of CQ prevents development past the intra-erythrocytic trophozoite stage (red arrows). (C) The p52⁻/p36⁻ GAP knockout results in very early liver stage arrest before formation of the parasitophorous vacuole (red arrow). Modified from ref. 45.