Antibodies to the N-Terminal Block 2 of<i>Plasmodium falciparum</i>Merozoite Surface Protein 1 Are Associated with Protection against Clinical Malaria

Cavanagh, David; Dodoo, Daniel; Hviid, Lars; Kurtzhals, Jørgen A. L.; Theander, Thor G.; Akanmori, Bartholomew D.; Polley, Spencer D.; Conway, David J.; Koram, Kojo; McBride, Jana S.

doi:10.1128/iai.72.11.6492-6502.2004

Cited by 96 publications

(113 citation statements)

References 42 publications

(58 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Antibodies against MSP1-19 were also predominantly of the IgG1 and IgG3 isotypes, in agreement with the results of previous studies from countries in Africa where malaria is endemic (14,22). In some studies, scientists have found that high levels of anti-MSP1 IgG1 antibodies are associated with protection against malaria attacks (22), whereas in other studies, the scientists failed to observe such an association (19).…”

Section: Discussionsupporting

confidence: 79%

Humoral Responses toPlasmodium falciparumBlood-Stage Antigens and Association with Incidence of Clinical Malaria in Children Living in an Area of Seasonal Malaria Transmission in Burkina Faso, West Africa

et al. 2008

Self Cite

View full text Add to dashboard Cite

There is longstanding evidence that immunoglobulin G (IgG) has a role in protection against clinical malaria, and human antibodies of the cytophilic subclasses are thought to be particularly critical in this respect. In this cohort study, 286 Burkinabè children 6 months to 15 years old were kept under malaria surveillance in order to assess the protective role of antibody responses against four antigens which are currently being evaluated as vaccine candidates: apical membrane antigen 1 (AMA1), merozoite surface protein 1-19 (MSP1-19), MSP3, and glutamate-rich protein (GLURP). Total IgG, IgM, and IgG subclass responses were measured just before the malaria transmission season. The incidence of malaria was 2.4 episodes per child year of risk. After adjusting for the confounding effects of age, the level of total IgG to GLURP was strongly associated with reduced malaria incidence (incidence rate ratio associated with a doubling of total IgG, 0.79; 95% confidence interval, 0.66 to 0.94; P ‫؍‬ 0.009.); there was a borderline statistically significant association between the level of total IgG to MSP3 and malaria incidence and no evidence of an association for total IgG to AMA1 and to MSP1-19. Of the IgG subclass responses studied, only IgG3 and IgG4 against GLURP and IgG1 against AMA1 were associated with reduced risk of clinical malaria. There was no evidence of an interaction between responses to AMA1 and baseline parasitemia in their effects on malaria incidence. Currently included in malaria vaccine formulations for clinical trials in humans, these blood-stage antigens, AMA1 and GLURP, offer good prospects for malaria vaccine development.In sub-Saharan Africa, the clinical manifestations of malaria are caused by asexual blood stages of Plasmodium falciparum, and antigens on asexual parasite stages in the bloodstream are critical in the development of protective immunity to the disease. After repeated exposure, nonsterile immunity to malaria can be acquired by people living in areas of endemicity. Strong evidence exists, from the passive transfer of antibodies between immune and nonimmune individuals, that this immunity can be antibody mediated (18,29,40). The most efficient in vivo model for this antibody-mediated parasite control in areas where the disease is endemic requires the participation of monocytes and has been called antibody-dependent cellular inhibition (ADCI) (24,26). This assay is assumed to mimic the in vivo cooperation between monocytes and cytophilic parasite-specific antibodies and is considered a surrogate marker of immunity against P. falciparum blood stages (21). BouharounTayoun and Druilhe observed profound differences in the distribution of immunoglobulin (Ig) subclasses between clinically protected and susceptible individuals, with cytophilic subclasses (immunoglobulin G1 [IgG1] and IgG3) being dominant in protected individuals (10). In different epidemiological settings, similar findings have been made, underscoring the importance of cytophilic antibodies against blood-stage antigens in ...

show abstract

Section: Discussionsupporting

confidence: 79%

Humoral Responses toPlasmodium falciparumBlood-Stage Antigens and Association with Incidence of Clinical Malaria in Children Living in an Area of Seasonal Malaria Transmission in Burkina Faso, West Africa

et al. 2008

Self Cite

View full text Add to dashboard Cite

show abstract

“…Thus, early studies have demonstrated the presence of naturally acquired antibodies against the N terminus (7, 9) and C terminus (13,28,31) of PfMSP1. The presence of such naturally acquired antibodies against MSP1 was later correlated to clinical protection in some, though not all, studies (8,10,12,14,24,25,26). Although the role of other portions of this large molecule remains mostly unknown, these studies have validated the N and C termini of PfMSP1 as solid subunit vaccine candidates against P. falciparum.…”

mentioning

confidence: 86%

“…personally diagnosed these patients, and after obtaining ethical consent to not treat them with drugs, actively followed them up twice a week for 2 months to guarantee that they did not develop malaria symptoms. Moreover, we analyzed independently the N and C termini of PvMSP1, as antibodies against both regions of the MSP1 of P. falciparum have been associated with clinical protection and acquired immunity (8,10,12,14,24,25,26). Strikingly, in spite of being the most immunogenic portion of PvMSP1 in natural infections and being capable of boosting (34), there was no association of antibody responses against the C terminus of PvMSP1 in survey A with clinical protection or risk of P. vivax infection (Fig.…”

Section: Discussionmentioning

confidence: 99%

A Reduced Risk of Infection with Plasmodium vivax and Clinical Protection against Malaria Are Associated with Antibodies against the N Terminus but Not the C Terminus of Merozoite Surface Protein 1

et al. 2006

View full text Add to dashboard Cite

Progress towards the development of a malaria vaccine against Plasmodium vivax, the most widely distributed human malaria parasite, will require a better understanding of the immune responses that confer clinical protection to patients in regions where malaria is endemic. The occurrence of clinical protection in P. vivax malaria in Brazil was first reported among residents of the riverine community of Portuchuelo, in Rondônia, western Amazon. We thus analyzed immune sera from this same human population to determine if naturally acquired humoral immune responses against the merozoite surface protein 1 of P. vivax, PvMSP1, could be associated with reduced risk of infection and/or clinical protection. Our results demonstrated that this association could be established with anti-PvMSP1 antibodies predominantly of the immunoglobulin G3 subclass directed against the N terminus but not against the C terminus, in spite of the latter being more immunogenic and capable of natural boosting. This is the first report of a prospective study of P. vivax malaria demonstrating an association of reduced risk of infection and clinical protection with antibodies against an antigen of this parasite.Malaria remains one of the major public health problems in South and Central America, where Plasmodium vivax is the main species responsible for infections. Although malaria caused by this human parasite is not lethal, the clinical manifestations represent a major socioeconomical burden in the major cities and rural areas of the Brazilian Amazon, which contains 99.7% of all malaria cases. Although a few studies indicate that some cross-protection between Plasmodium vivax, the most widely distributed human malaria parasite, and P. falciparum, the most virulent species, does occur (33), immunity in malaria is mostly species specific; thus, it is likely that a vaccine against P. falciparum will not cross-protect against P. vivax. Progress is being made to develop P. vivax vaccines per se (for a review, see reference 2); however, to date there are no prospective studies associating human immune responses to any P. vivax antigen with clinical protection.The history of malaria in Brazil has been punctuated with epidemics associated with migration movements of nonimmune population to areas where malaria is endemic (20,30,36). Previous studies done in these epidemiological settings showed that Plasmodium infection was always associated with symptoms, and clinical protection was not observed (27). However, through a cross-sectional and longitudinal study among native Amazon residents of the riverine community of Portuchuelo in Rondônia, located in the western Brazilian Amazon, the occurrence of symptomless Plasmodium vivax-infected individuals was reported (1, 6). Symptomless Plasmodium infections were defined as individuals who contain parasites in their peripheral blood, as detected by Giemsa blood smears and/or PCR, and who were not drug treated yet did not develop clinical symptoms during a 2-month individual follow-up. These rigorous criteria...

show abstract

“…Antibodies which bind Fc receptors and mediate antibody-dependent cytotoxicity, growth inhibition, or phagocytosis (so-called "cytophilic" antibodies) have repeatedly been shown to be highly effective at clearing blood stage malaria parasites, both in humans (14,43) and in mice (36,38,55). In humans, immunoglobulin G3 (IgG3) is especially valuable in this regard (4,19), and the presence of IgG3 to various merozoite-associated antigens has been linked to protective immunity in seroepidemiological studies (10,15,35,51,56).…”

mentioning

confidence: 99%

Epitope-Specific Regulation of Immunoglobulin Class Switching in Mice Immunized with Malarial Merozoite Surface Proteins

Tongren

Corran

Jarra³

et al. 2005

Infect Immun

View full text Add to dashboard Cite

Antibodies that bind to Fc receptors and activate complement are implicated in the efficient control of pathogens, but the processes that regulate their induction are still not well understood. To investigate antigen-dependent factors that regulate class switching, we have developed an in vivo model of class switching to immunoglobulin G2b (IgG2b) using the malaria antigen Plasmodium falciparum merozoite surface protein 2 (MSP2). C57BL/6 mice were immunized with recombinant proteins representing discrete domains of MSP2, and a T-cell epitope (C8) was identified within the conserved C terminus of the protein that preferentially induces IgG2b antibodies. The ability of C8 to induce IgG2b is ablated in both homozygous gamma interferonnegative and interleukin 10-negative mice. The IgG2b-inducing properties of C8 override the IgG1-inducing properties of both the fusion protein partner, glutathione S-transferase, and the adjuvant. Furthermore, when attached to other proteins that normally induce IgG1 responses, C8 induces a switch to IgG2b secretion. This is the first description of a defined T-cell epitope that drives specific IgG2b subclass switching, and our data offer proof of the concept that chimeric vaccines incorporating specific T-cell "switch epitopes" might be used to enhance qualitative aspects of the antibody response.

show abstract

Antibodies to the N-Terminal Block 2 ofPlasmodium falciparumMerozoite Surface Protein 1 Are Associated with Protection against Clinical Malaria

Cited by 96 publications

References 42 publications

Humoral Responses toPlasmodium falciparumBlood-Stage Antigens and Association with Incidence of Clinical Malaria in Children Living in an Area of Seasonal Malaria Transmission in Burkina Faso, West Africa

Humoral Responses toPlasmodium falciparumBlood-Stage Antigens and Association with Incidence of Clinical Malaria in Children Living in an Area of Seasonal Malaria Transmission in Burkina Faso, West Africa

A Reduced Risk of Infection with Plasmodium vivax and Clinical Protection against Malaria Are Associated with Antibodies against the N Terminus but Not the C Terminus of Merozoite Surface Protein 1

Epitope-Specific Regulation of Immunoglobulin Class Switching in Mice Immunized with Malarial Merozoite Surface Proteins

Contact Info

Product

Resources

About