Clinical immunity to malaria.

Under appropriate conditions of transmission intensity, functional immunity to malaria appears to be acquired in distinct stages. The first phase reduces the likelihood of severe or fatal disease; the second phase limits the clinical impact of 'mild' malaria; and the third provides partial but incomplete protection against pathogen burden. These findings suggest clinical immunity to mortality and morbidity is acquired earlier, with greater ease, and via distinct mechanisms as compared to anti-parasite immunity, which is more difficult to achieve, takes longer and is only ever partially efficacious. The implications of this view are significant in that current vaccination strategies aim predominantly to achieve anti-parasite immunity, although imparting clinical immunity is the public health objective. Despite enormous relevance for global public health, the mechanisms governing these processes remain obscure. Four candidate mechanisms might mediate clinical immunity, namely immunity to cytoadherence determinants, tolerance to toxins, acquired immunity to toxins, and immunoregulation. This review addresses the targets and determinants of clinical immunity, and considers the implications for vaccine development.

[1]  A. Ferrante,et al.  Atypical IgG subclass antibody responses to Plasmodium falciparum asexual stage antigens. , 1997, Parasitology today.

[2]  A. Ferrante,et al.  Humoral immune responses of Solomon Islanders to the merozoite surface antigen 2 of Plasmodium falciparum show pronounced skewing towards antibodies of the immunoglobulin G3 subclass , 1997, Infection and immunity.

[3]  W. Hawley,et al.  Natural immune response to the C-terminal 19-kilodalton domain of Plasmodium falciparum merozoite surface protein 1 , 1996, Infection and immunity.

[4]  E. Riley,et al.  Selective recognition of malaria antigens by human serum antibodies is not genetically determined but demonstrates some features of clonal imprinting. , 1996, International immunology.

[5]  C. Rogier,et al.  Pattern of immunoglobulin isotype response to Plasmodium falciparum blood-stage antigens in individuals living in a holoendemic area of Senegal (Dielmo, west Africa). , 1996, The American journal of tropical medicine and hygiene.

[6]  A. Holder,et al.  Clinical immunity to Plasmodium falciparum malaria is associated with serum antibodies to the 19-kDa C-terminal fragment of the merozoite surface antigen, PfMSP-1. , 1996, The Journal of infectious diseases.

[7]  E. Riley,et al.  Human antibody response to Plasmodium falciparum merozoite surface protein 2 is serogroup specific and predominantly of the immunoglobulin G3 subclass , 1995, Infection and immunity.

[8]  M. Alpers,et al.  Assessment of the role of the humoral response to Plasmodium falciparum MSP2 compared to RESA and SPf66 in protecting Papua New Guinean children from clinical malaria , 1995, Parasite immunology (Print).

[9]  J. Baird.  Host age as a determinant of naturally acquired immunity to Plasmodium falciparum. , 1995, Parasitology today.

[10]  A. Holder,et al.  Serum antibodies from malaria-exposed people recognize conserved epitopes formed by the two epidermal growth factor motifs of MSP1(19), the carboxy-terminal fragment of the major merozoite surface protein of Plasmodium falciparum , 1995, Infection and immunity.

[11]  M. Alpers,et al.  Humoral and cell-mediated immunity to the Plasmodium falciparum ring-infected erythrocyte surface antigen in an adult population exposed to highly endemic malaria , 1995, Infection and immunity.

[12]  J. V. D. van de Winkel,et al.  Human IgG Fc receptor heterogeneity: molecular aspects and clinical implications. , 1993, Immunology today.

[13]  E. Riley,et al.  Immunoglobulin M and G antibody responses to Plasmodium falciparum glutamate-rich protein: correlation with clinical immunity in Gambian children , 1993, Infection and immunity.

[14]  C. Snapper,et al.  Towards a comprehensive view of immunoglobulin class switching. , 1993, Immunology today.

[15]  A. Holder,et al.  Naturally acquired cellular and humoral immune responses to the major merozoite surface antigen (Pf MSP1) of Plasmodium falciparum are associated with reduced malaria morbidity , 1992, Parasite immunology.

[16]  P. Druilhe,et al.  Plasmodium falciparum malaria: evidence for an isotype imbalance which may be responsible for delayed acquisition of protective immunity , 1992, Infection and immunity.

[17]  R. Anders,et al.  Failure of recombinant vaccinia viruses expressing Plasmodium falciparum antigens to protect Saimiri monkeys against malaria , 1991, Infection and immunity.

[18]  K. Marsh,et al.  Naturally acquired immunity to Plasmodium falciparum. , 1991, Immunology today.

[19]  A. Thomas,et al.  Sequence comparison of allelic forms of the Plasmodium falciparum merozoite surface antigen MSA2. , 1990, Molecular and biochemical parasitology.

[20]  A. Sabchareon,et al.  Antibodies that protect humans against Plasmodium falciparum blood stages do not on their own inhibit parasite growth and invasion in vitro, but act in cooperation with monocytes , 1990, The Journal of experimental medicine.

[21]  R. Levinsky,et al.  Branhamella catarrhalis: antigenic determinants and the development of the IgG subclass response in childhood. , 1990, The Journal of infectious diseases.

[22]  S. Lindsay,et al.  Recognition of dominant T cell-stimulating epitopes from the circumsporozoite protein of Plasmodium falciparum and relationship to malaria morbidity in Gambian children. , 1990, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[23]  R. Coppel,et al.  Structural diversity in the 45-kilodalton merozoite surface antigen of Plasmodium falciparum. , 1990, Molecular and biochemical parasitology.

[24]  R. Ramasamy,et al.  Characterisation of an inhibitory monoclonal antibody-defined epitope on a malaria vaccine candidate antigen. , 1990, Immunology letters.

[25]  H. Groux,et al.  Opsonization as an effector mechanism in human protection against asexual blood stages of Plasmodium falciparum: functional role of IgG subclasses. , 1990, Research in immunology.

[26]  S. Donachie,et al.  46-53 kilodalton glycoprotein from the surface of Plasmodium falciparum merozoites. , 1989, Molecular and biochemical parasitology.

[27]  J. Adams,et al.  Limited immunological recognition of critical malaria vaccine candidate antigens. , 1988, Science.

[28]  P. Byass,et al.  Mortality and morbidity from malaria among children in a rural area of The Gambia, West Africa. , 1987, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[29]  S. Khusmith,et al.  Epidemiological correlation between levels of antibodies promoting merozoite phagocytosis of Plasmodium falciparum and malaria-immune status , 1987, Infection and immunity.

[30]  D. Wara,et al.  Development of serum IgG subclass levels in children. , 1986, Monographs in allergy.

[31]  H. Spiegelberg,et al.  Biological activities of immunoglobulins of different classes and subclasses. , 1974, Advances in immunology.