Malaria: Prevention, vaccination

It has been possible to protect humans against malaria by vaccinating them with irradiated sporozoites. This method is not practical, however, on a large scale. To date there is still no effective vaccine available. Research into a vaccine is based on a number of possibilities. An immune response can be triggered against sporozoites, against liver forms, against erythrocytic forms and/or against gametocytes but this does not necessarily have a protective effect. An effective malaria vaccine is not likely to be developed in the foreseeable future.

SPf66

Most initial work in developing a vaccine was carried out by studying the proteins found in sporozoites (circumsporozoite surface protein). The idea was that stimulated antibodies, aimed at invariant repetitive amino acid sequences which occur in natural proteins, would eliminate the sporozoites, in the hope of preventing infection (stopping the infection before the liver phase). The repetitive sequences have little or no immunogenicity, however, because they are similar to proteins which are present naturally in the human body. Even if antibodies can be produced, sporozoites only remain in the circulation for 30 minutes. There is therefore little time to neutralise all parasites by means of antibodies. Still, experiments were irradiated sporozoites were used as antigen showed important protection. If sporozoites could be cultured en masse, this would be a watershed. Another route was followed in the development of a cocktail of synthetic antigens. In 1987 Manuel Patarroyo (Colombia) demonstrated that a synthetic peptide vaccine (SPf66) is immunogenic and protects Aotus monkeys against challenge infection with P. falciparum. It also proved safe and partially protective in test subjects in Latin America. It was subsequently tested (double-blind, randomised and placebo-controlled), first in La Tola, Colombia (39% effectiveness) and then (independently) in Idete and Kilombero, Tanzania, regions with high transmission, and in Gambia. In 1994 the results became known. The effectiveness of 3 injections against clinical malaria was 31% (Tanzania) and 0% (Gambia) and the incidence of parasitaemia was the same in test subjects as in the control group. There was no adequate pre-erythrocytic immunity. Other later trials were equally disappointing.

RTS,S

In 1997 the first favourable results became known of a vaccine formed from a fusion protein of

• part of the circumsporozoite antigen of P. falciparum (called RTS, a polypeptide consisting of amino acids 207-395) and

• hepatitis B Surface Antigen (HBSAg) (a protein chain with 226 amino acids). The vaccine was administered with an adjuvant (AS02). The new product is at present still in the experimental phase. The initial results suggest a safe, immunogenic pre-erythrocytic vaccine which offers significant protection against natural P. falciparum infection.

  A randomised and controlled study in the Gambia on 306 volunteers showed RTS,S/AS02 to be safe, immunogenic, and to provide significant protection against natural P. falciparum infection. Larger trials are being planned.

Category: Medicine Notes