Naturally acquired immunoglobulin (Ig)G subclass antibodies to crude asexual <i>Plasmodium falciparum</i> lysates: evidence for association with protection for IgG1 and disease for IgG2

Ndungu, Francis M.; Bull, Peter C.; Ross, Amanda; Lowe, Brett; Kabiru, Ephantus W.; Marsh, Kevin

doi:10.1046/j.0141-9838.2001.00440.x

Cited by 81 publications

(79 citation statements)

References 24 publications

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“…Another aspect of particular note concerns the detection of the anti-VSA antibodies of all four IgG isotypes, in the case of some isolates at very similar levels, which is consistent with an earlier report (23). The antibody response to crude parasite antigen preparations commonly comprises a mixture of all four IgG isotypes, but the response to defined P. falciparum asexual-stage antigens is usually more restricted and is dominated by cytophilic isotypes (4,18,41,57). In the profile that we observed here, IgG3 antibodies did predominate, although they were equivalent to IgG4 in children in terms of magnitude and equivalent to IgG2 in adults in terms of the IRR.…”

Section: Discussionsupporting

confidence: 69%

Immunoglobulin G Isotype Responses to Variant Surface Antigens ofPlasmodium falciparumin Healthy Gabonese Adults and Children during and after Successive Malaria Attacks

et al. 2004

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We assessed immunoglobulin G (IgG) isotype responses with specificity for the variant surface antigens (VSA) of heterologous Plasmodium falciparum isolates by using flow cytometry and plasma from healthy Gabonese adults and from children during and after two consecutive malaria episodes. The individual isolate-specific antibody profiles differed markedly in terms of their isotype content but were similar for healthy adults and healthy uninfected children. In healthy adults, IgG3 and IgG2 responses were the highest, while in healthy children, IgG3 and IgG4 predominated. A transiently elevated IgG1 response was observed during the second of two successive malaria episodes in children, signaling P. falciparum infection-induced cross-reactive anti-VSA responses. Our findings highlight the prominence of IgG3 in the overall profile of these responses but also indicate a marked age-related increase in the prevalence of anti-VSA antibodies of the classically noncytophilic IgG2 isotype, possibly reflecting the high frequency of the histidine-131 variant of Fc␥RIIA in the Gabonese population.

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Section: Discussionsupporting

confidence: 69%

Immunoglobulin G Isotype Responses to Variant Surface Antigens ofPlasmodium falciparumin Healthy Gabonese Adults and Children during and after Successive Malaria Attacks

et al. 2004

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“…Most importantly, both adjuvants led to generation of cytophilic antibodies (mainly IgG1) (i.e., isotypes capable of supporting in vitro and in vivo antibody-dependent, monocyte-mediated parasite growth inhibition). Indeed, IgG1 and IgG3 anti-plasmodium antibodies, but not IgG2, IgG4, and IgM anti-plasmodium antibodies (1,32) or anti-MSP3 antibodies (40), have been associated with protection in humans, as well as in primates, and to be the key players of ADCI (6,8,15,(33)(34)(35). We also showed that these antibodies were also able to bind a nonsynthetic recombinant MSP3 molecule (rMSP3 210-380).…”

Section: Vol 73 2005mentioning

confidence: 74%

“…However, the Montanide formulation led to the withdrawal of an unacceptably high number of volunteers with severe local reactions, whereas the aluminum hydroxide formulation was generally well tolerated. The largely cytophilic IgG1 anti-MSP-3-specific profile of the humoral response may confer to the vaccine potential monocyte-mediated protective activity (1,32,40). This should be addressed in endemic area trials or with individuals exposed to malaria challenges.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, IgG cooperates with monocytes in a mechanism of antibody-dependent inhibition of parasite growth (ADCI) in vitro (6,8,15). Protected individuals produce mostly cytophilic antimalaria antibodies (IgG1 or IgG3), whereas nonprotected subjects produce mostly IgG2 and IgM (1,32,40). The C-terminal region of MSP3, which is highly conserved in various P. falciparum isolates, was identified as the target of these biologically active antibodies (33,34,39).…”

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confidence: 99%

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Phase I Malaria Vaccine Trial with a Long Synthetic Peptide Derived from the Merozoite Surface Protein 3 Antigen

et al. 2005

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“…Studies with humans have found a correlation between IgG1 and IgG3 levels and protection against severe disease (7,18,35); these two antibody isotypes have also been shown to be capable of mediating opsonization (20). Furthermore, passive transfer of malariaspecific IgG has been shown to reduce parasitemia in humans (8,11,40).…”

Section: Discussionmentioning

confidence: 99%

Secreted Antibody Is Required for Immunity toPlasmodium berghei

2009

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Infection with Plasmodium berghei is lethal to mice, causing high levels of parasitemia, severe anemia, and death. However, when mice are treated with antimalarial drugs during acute infection, they have enhanced immunity to subsequent infections. With this infection and cure model of immunity, we systematically examined the basis of adaptive immunity to infection using immunodeficient mice. In order to induce adaptive immunity, mice were infected with blood-stage parasites. When the mice developed 2 to 3% parasitemia, they were treated with chloroquine to cure the infection. These convalescent mice were then challenged with homologous blood-stage parasites. Immunized wild-type mice were able to control the level of infection. In contrast, mice lacking mature B cells and T cells were unable to control a challenge infection, indicating the critical role of lymphocytes in immunity to P. berghei. Furthermore, mice lacking secreted antibody were unable to control the level of parasitemia following a challenge infection. Our results indicate that secreted antibody is a requirement for immunity to P. berghei.Each year there are approximately 500 million cases of malaria worldwide, resulting in 2 to 3 million deaths, primarily in children in sub-Saharan Africa (42). Malaria is caused by infection with one of four protozoan Plasmodium species: P. falciparum, P. vivax, P. malariae, and P. ovale. P. falciparum is responsible for the majority of severe disease, which can manifest itself in anemia, cerebral malaria, organ failure, and death. Repeated infection and treatment of individuals in areas of malaria endemicity eventually induce a level of immunity that limits morbidity and results in chronic infection with low levels of parasitemia (41). A fully effective vaccine that reduces parasite burden and severe disease has not been developed.Murine models of malaria have long been used to examine the immune response to Plasmodium parasites and to understand the host factors required for the development of immunity. P. berghei infection in mice is lethal, causing high levels of parasitemia, severe anemia, and body weight loss. However, mice can become resistant to subsequent infections by treatment with antimalarial drugs during acute infection (27). This is known as the infection and cure model, and mice that develop this immunity mimic the human experience of disease in that they are reinfected but experience low-level patent parasitemia and survive. However, it takes years to establish this level of immunity in humans (36), while in mice it is accomplished by only one infection and drug cure, which provides long-lasting protection (12,13,48). An understanding of the basis of rodent immunity to blood-stage infection will help to direct future vaccine approaches.The fact that immunity induced by infection and cure is long-lasting suggests that the adaptive immune system is required for immunity. Evidence from previous work indicates a role for B and T cells in immunity. Mice lacking both mature B and T cells (SCID mice) (6)...

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Naturally acquired immunoglobulin (Ig)G subclass antibodies to crude asexual Plasmodium falciparum lysates: evidence for association with protection for IgG1 and disease for IgG2

Cited by 81 publications

References 24 publications

Immunoglobulin G Isotype Responses to Variant Surface Antigens ofPlasmodium falciparumin Healthy Gabonese Adults and Children during and after Successive Malaria Attacks

Immunoglobulin G Isotype Responses to Variant Surface Antigens ofPlasmodium falciparumin Healthy Gabonese Adults and Children during and after Successive Malaria Attacks

Phase I Malaria Vaccine Trial with a Long Synthetic Peptide Derived from the Merozoite Surface Protein 3 Antigen

Secreted Antibody Is Required for Immunity toPlasmodium berghei

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