Tài liệu Báo cáo khoa học: Vaccines against malaria – an update doc

MINIREVIEW

Vaccines against malaria – an update

Kai Matuschewski1 and Ann-Kristin Mueller1,2

1 Department of Parasitology, Heidelberg University School of Medicine, Germany

2 Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK

Malaria is a preventable and treatable vector-borne

infectious disease that is caused by single-cell eukary￾otic parasites of the genus Plasmodium. According to

recent estimates by the World Health Organization

(WHO), malaria remains one of the major causes of

mortality and morbidity, with 3.2 billion people at

risk, 300–500 million clinical cases and more than one

million deaths annually, particularly in young children

in sub-Saharan Africa [1].

Plasmodium transmission occurs by the injection of

infectious sporozoites during the probing phase for a

blood meal by an infected female Anopheles mosquito

[2]. Sporozoites actively move away from the site of

injection, enter a capillary and within minutes reach

the liver where they transform into liver stages and

commit to continuous replication resulting in the

generation of tens of thousands of pathogenic merozo￾ites [3]. Malaria-associated pathology is exclusively

restricted to the asexual replication of the parasite

within erythrocytes, a rather unique environment for

an intracellular pathogen. This terminally differenti￾ated host cell offers the advantage of complete absence

of MHC I-restricted antigen presentation, and, hence

cellular immunity against the host cell. Protective

mechanisms operate by neutralizing antibodies

against the merozoite surface proteins and surface

Keywords

attenuated live parasite; malaria; MSP1;

Plasmodium; protective immunity; RTS ⁄ S;

severe disease; transmission-blocking

antibodies; vaccine; var2CSA

Correspondence

K. Matuschewski, Department of

Parasitology, Heidelberg University School

of Medicine, Im Neuenheimer Feld 324,

69120 Heidelberg, Germany

Fax: +49 6221 564643

Tel: +49 6221 568284

E-mail: Kai.Matuschewski@med.

uni-heidelberg.de

(Received 27 May 2007, accepted 19 July

2007)

doi:10.1111/j.1742-4658.2007.05998.x

Malaria vaccine discovery and development follow two principal strategies.

Most subunit vaccines are designed to mimic naturally acquired immunity

that develops over years upon continuous exposure to Plasmodium trans￾mission. Experimental model vaccines, such as attenuated live parasites

and transmission-blocking antigens, induce immune responses superior to

naturally acquired immunity. The promises and hurdles of the different

tracks towards an effective and affordable vaccine against malaria are dis￾cussed.

Abbreviations

CSP, circumsporozoite protein; FMP1, falciparum malaria protein-1; GAP, genetically attenuated parasite; MSP1, merozoite surface protein 1;

PfEMP1, Plasmodium falciparum erythrocyte membrane protein 1; Pfs25, Plasmodium falciparum surface protein with apparent molecular

mass of 25 kDa; RTS ⁄ S, recombinant P. falciparum CSP vaccine, which includes the central repeat sequence ‘R’ and major T-cell epitopes

‘T’, fused to the entire hepatitis B surface antigen ‘S’ and coexpressed in yeast with the ‘S’ antigen; TRAP, thrombospondin-related

anonymous protein; var2CSA, variant surface antigen 2, chondroitin sulphate A-binding.

4680 FEBS Journal 274 (2007) 4680–4687 ª 2007 The Authors Journal compilation ª 2007 FEBS