Research Article: Towards a Vaccine against Plasmodium vivax Malaria

Date Published: December 18, 2007

Publisher: Public Library of Science

Author(s): James G Beeson, Brendan S Crabb

Abstract: The authors discuss a new study that suggests thatPlasmodium vivax Duffy-binding protein could be a candidate antigen for developing aP. vivax vaccine.

Partial Text: There is little doubt that effective interventions against Plasmodium vivax are needed. An estimated 2.6 billion people live in areas endemic for P. vivax [1], and P. vivax carries a substantial burden of disease with 50–70 million clinical episodes each year [2].

Effective malaria vaccines could act by preventing initial liver-stage infection and/or blood-stage replication of parasites. The attraction of targeting blood stages is that it is during these stages that disease occurs. Although Plasmodium parasites initially infect hepatocytes, this pre-erythrocytic stage of malaria infection passes silently without any illness, and disease results from unrestricted replication of parasites in the blood. Vaccines targeting the blood stage may not have to induce sterile immunity (immunity that prevents infection per se), which is challenging to achieve; effective control of parasite replication may be sufficient to prevent illness and complications, as observed with naturally acquired immunity.

One antigen that stands out as an excellent vaccine candidate for P. vivax is Duffy-binding protein (DBP). In a new study published in this issue of PLoS Medicine, Brian Grimberg and colleagues provide important data to support further research on this antigen as a possible vaccine candidate [3].

Antibodies to merozoite antigens of malaria are thought to play an important role in acquired immunity, and may act by inhibiting erythrocyte or reticulocyte invasion and subsequent replication of parasites. However, data on the inhibitory activity of antibodies are limited, particularly for P. vivax.

Should a vaccine targeted to PvDBP now go forward to a phase I trial? Although PvDBP is a rational vaccine choice, there remain important issues to address. An effective vaccine may need to overcome significant antigenic diversity in PvDBP. Grimberg and colleagues report that anti-PvDBP antibodies bound at similar levels to two different PvDBP variants. However, it will be important to extend this work to evaluate the effect of polymorphism on antibody inhibition. Others reported that some polymorphisms did affect the activity of antibodies that inhibit binding of PvDBP to DARC [15].



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