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      Malaria vaccine: roadblocks and possible solutions

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          Abstract

          Malaria remains the most prevalent and devastating parasitic disease worldwide. Vaccination is considered to be an approach that will complement other strategies for prevention and control of the disease in the future. In the last 10 years, intense studies aimed at the development of a malaria vaccine have provided important knowledge of the nature of the host immunological mechanisms of protection and their respective target antigens. It became well established that protective immune responses can be generated against the distinct stages of Plasmodium. However, in general, protective immune responses are directed at stage-specific antigens. The elucidation of the primary structure of these antigens made possible the generation of synthetic and recombinant proteins that are being extensively used in experimental immunizations against the infection. Today, several epitopes of limited polymorphism have been described and protective immunity can be generated by immunization with them. These epitopes are being tested as primary candidates for a subunit vaccine against malaria. Here we critically review the major roadblocks for the development of a malaria vaccine and provide some insight on how these problems are being solved

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          Most cited references72

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          Randomised trial of efficacy of SPf66 vaccine against Plasmodium falciparum malaria in children in southern Tanzania.

          Effective, safe antimalarial vaccines have proved elusive. The synthetic polypeptide SPf66 vaccine is based on preerythrocytic and asexual blood-stage proteins of Plasmodium falciparum. We report here a randomised double-blind placebo-controlled trial of the efficacy of the SPf66 vaccine against clinical P falciparum malaria in idete, southern Tanzania, an area of intense perennial malaria transmission. 586 children aged 1-5 years received three doses of vaccine (n = 274) or placebo (n = 312). The incidence and density of parasitaemia were assessed through repeated cross-sectional surveys on subgroups of children. Morbidity was monitored over a 1 year period through passive case detection in all children plus active case detection in a subgroup of 191. An episode of clinical malaria was defined as measured fever (> or = 37.5 degrees C) and parasite density > 20,000/microL. No severe side-effects were seen and the frequency of mild side-effects after the third dose was less than 6%. The vaccine was highly immunogenic and after three doses all vaccine recipients had detectable anti-SPf66 antibodies: the geometric mean index of response was 8.3 in the vaccine group and 0.7 in the placebo group. The incidence of parasitaemia was similar in both groups. 123 children had at least one episode of clinical malaria during the follow-up period after the third dose and annual incidence rates were 0.25 in the vaccine group and 0.35 in the placebo group. Estimated vaccine efficacy was 31% (95% confidence interval 0-52%; p = 0.046). After the third dose there were 6 deaths among the study cohort (1 vaccine, 5 placebo). This study confirms that SPf66 is safe, immunogenic and reduces the risk of clinical malaria among children exposed to intense P falciparum transmission.
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            Merozoite surface coat precursor protein completely protects Aotus monkeys against Plasmodium falciparum malaria.

            Groups of Aotus (owl) monkeys were immunized with either the Plasmodium falciparum merozoite surface-coat precursor protein and its processing fragments or a complex of high molecular mass rhoptry proteins and challenged with a lethal infection of the homologous P. falciparum Uganda Palo Alto (FUP) strain. No patent parasitemia could be detected on thick blood films of monkeys immunized with the merozoite surface antigens; however, only one of three monkeys immunized with the rhoptry proteins was partially protected, while two required drug therapy. The experiment clearly demonstrates that the merozoite surface-coat precursor protein can completely protect Aotus monkeys against a lethal infection of the human malaria parasite.
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              Monoclonal antibodies that inhibit Plasmodium falciparum invasion in vitro recognise the first growth factor-like domain of merozoite surface protein-1.

              A major protein found on the surface of the invasive stage of the malaria parasite Plasmodium falciparum, merozoite surface protein-1 (MSP1), has been proposed as a vaccine candidate. Antibodies which recognise a single fragment of this molecule (MSP1(19)), composed of 2 regions related to epidermal growth factor (EGF), also inhibit parasite growth in vitro. It is shown by direct expression of the individual EGF-like domains in Escherichia coli, that the first domain is the target of growth-inhibitory antibodies. A single amino acid difference influences the binding of some antibodies to this domain.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Journal
                bjmbr
                Brazilian Journal of Medical and Biological Research
                Braz J Med Biol Res
                Associação Brasileira de Divulgação Científica (Ribeirão Preto )
                1414-431X
                March 1998
                : 31
                : 3
                : 317-332
                Affiliations
                [1 ] Universidade Federal do Pará Brazil
                [2 ] Universidade Federal de São Paulo
                Article
                S0100-879X1998000300002
                10.1590/S0100-879X1998000300002
                d74a8bd0-3918-47de-ac4b-bbb6a98a7250

                http://creativecommons.org/licenses/by/4.0/

                History
                Product

                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=0100-879X&lng=en
                Categories
                BIOLOGY
                MEDICINE, RESEARCH & EXPERIMENTAL

                Medicine,General life sciences
                malaria,Plasmodium,vaccine,immunity,infectious disease
                Medicine, General life sciences
                malaria, Plasmodium, vaccine, immunity, infectious disease

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