Monoclonal antibodies identify the protective antigens of sporozoites of Plasmodium knowlesi.

Cochrane, Alan H.; Santoro, F; Nussenzweig, Victor; Gwadz, Robert W.; Nussenzweig, Ruth S.

doi:10.1073/pnas.79.18.5651

Cited by 87 publications

(76 citation statements)

References 13 publications

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“…In early studies, incubation of sporozoites of rodent, simian, or human species of Plasmodium with immune sera containing antirepeat antibodies led to loss of infectivity, as determined by the failure of the incubated sporozoites to induce a patent infection when injected into a susceptible host (12,42,46). Antirepeat antibodies neutralize sporozoite infectivity by blocking parasite-host cell interactions in the liver and inhibiting sporozoite motility required for hepatocyte invasion (8,57,59).…”

Section: Discussionmentioning

confidence: 99%

A Linear Peptide Containing Minimal T- and B-Cell Epitopes ofPlasmodium falciparumCircumsporozoite Protein Elicits Protection against Transgenic Sporozoite Challenge

et al. 2006

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An effective malaria vaccine is needed to address the public health tragedy resulting from the high levels of morbidity and mortality caused by Plasmodium parasites. The first protective immune mechanism identified in the irradiated sporozoite vaccine, the "gold standard" for malaria preerythrocytic vaccines, was sporozoiteneutralizing antibody specific for the repeat region of the surface circumsporozoite ( There is a critical need for an effective malaria vaccine, as standard public health measures have been eroded by drug resistance of the parasite and insecticide resistance of the mosquito vector. Moreover, traditional control measures have failed to prevent Plasmodium infections in 300 to 600 million people worldwide, resulting in over 1 million deaths each year (55). Vaccines remain the most cost-effective means for control of infectious diseases. Over the past 30 years, an effective malaria vaccine, based on attenuated sporozoites delivered by the bites of irradiated infected mosquitoes, has been shown to elicit sterile immunity in experimental animal models and human volunteers (11,25,27,45). However, large-scale production of an attenuated parasite vaccine faces significant practical limitations and logistical and regulatory hurdles that must be overcome. Sporozoites cannot be grown in culture and must be dissected from the salivary glands of infected mosquitoes that have fed on blood-stage parasites cultivated in human red blood cells. Additional challenges for attenuated sporozoite vaccines relate to cost, scale-up production, sterility, cold-chain storage, and route of immunization, which in humans has thus far been obtained only by exposure to the bites of irradiated infected mosquitoes. Nevertheless, the ability to elicit sterile protection following immunization with attenuated sporozoites provides a gold standard for development of subunit malaria vaccines that target the preerythrocytic stages of the parasite and effectively prevent initiation of the blood-stage infection responsible for clinical disease.In contrast to whole parasites, peptide vaccines can be readily synthesized from inexpensive, well-defined amino acid components and lyophilized for storage and transport. In recent years, peptide immunotherapeutics have been developed for human autoimmune diseases and allergies (21, 31), and peptide subunit vaccines for infectious diseases and treatment of cancer have been tested in clinical trials (3,24,32,33,52). The first phase I/II trial of a malaria synthetic peptide vaccine was carried out over 20 years ago to assess the efficacy of a peptide-protein conjugate vaccine, termed (NANP) 3 -TT, comprised of the immunodominant B-cell repeat epitope (NANP) 3 from the Plasmodium falciparum major surface circumsporozoite (CS) protein linked to tetanus toxoid (TT) as the protein carrier (26). Exposure of a small number of (NANP) 3 -TTimmunized volunteers to the bites of P. falciparum-infected mosquitoes demonstrated that the vaccine could elicit protective antibody responses against P. falciparum s...

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Section: Discussionmentioning

confidence: 99%

A Linear Peptide Containing Minimal T- and B-Cell Epitopes ofPlasmodium falciparumCircumsporozoite Protein Elicits Protection against Transgenic Sporozoite Challenge

et al. 2006

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“…The production and characterization of mAb against sporozoites of P. knowlesi, P. falciparum, and P. vivax are described elsewhere (4,5). The mAb were partially * Supported in part by grant DPE-0453-C-00-200 2-00 from the Agency for International Development, grant AI 17429 from the National Institutes of Health, and grants from the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Medicine and the Rockefeller Foundation.…”

Section: A T E R I a L S A N D M E T H O D Smentioning

confidence: 99%

“…T h e serum of protected animals reacts with the surface membrane of sporozoites and neutralizes their infectivity, which suggests that the effect of the vaccine is at least in part antibody mediated. T h e membrane-associated protective antigens of sporozoites of rodent (2,3), simian (4), and h u m a n (5) malaria have recently been identified by means of monoclonal antibodies (mAb). 1 They are stage-specific proteins that are distributed uniformly over the entire surface of the parasite and are shed when crosslinked by antibodies (3).…”

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“…T o investigate this phenomenon further we compare here the specificities of a series of m A b against CS proteins of parasites of monkey (P. knowlesi) and h u m a n (P. vivax and P. falciparum) malaria, including some that neutralized the infectivity of the sporozoites in vivo (4,5) or in vitro. 2 We present evidence that in every instance the m A b recognize the same unique region of the CS molecule, which contains at least two identical epitopes.…”

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Circumsporozoite proteins of malaria parasites contain a single immunodominant region with two or more identical epitopes.

Zavala

Cochrane

Nardin

et al. 1983

The Journal of Experimental Medicine

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299

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We have used panels of monoclonal antibodies to circumsporozoite (CS) proteins of Plasmodium falciparium, P. vivax, and P. knowlesi to determine the number of topographically independent epitopes of these antigens. The results of competition binding assays indicated that single regions of the CS molecules were recognized by the homologous monoclonal antibodies. Competition binding assays were also used to study the specificity of antibodies contained in the sera of humans and monkeys that had developed sterile immunity after immunization with irradiated, intact sporozoites. We found that single monoclonal antibodies inhibited 70-95% of the specific binding of the polyclonal antibodies to crude extracts of sporozoites. It appears, therefore, that CS proteins are among the most immunogenic constituents of sporozoites, and that a single region of these molecules contains most of the immunogenic activity. An additional finding was that the immunodominant region of CS molecules is multivalent with regard to the expression of a single epitope. This was demonstrated by the ability of monomers of CS proteins to bind simultaneously two or more molecules of the same monoclonal antibody.

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“…Immunological cross-reactivity is known to exist against the CS-proteins of unrelated species and this may be as a result of structural and functional similarities of the secondary and tertiary structures resulting in common epitopes. 23,[29][30][31] The objectives of this study were, firstly, to evaluate the exposure of wild African penguins to avian malaria during rehabilitation at SANCCOB by measuring anti-Plasmodium antibody levels using an ELISA similar to that of Graczyk et al 23 ; secondly, to determine the influence of these antibody levels on survival during rehabilitation and the effect of oiling on antibody levels and, finally, to show the effect of vector exclusion on the incidence of malaria-related deaths at SANCCOB.…”

Section: Introductionmentioning

confidence: 99%

Conservation implications of avian malaria exposure for African penguins during rehabilitation

Botes¹,

Thiart²,

Parsons³

et al. 2017

S. Afr. J. Sci.

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The African penguin (Spheniscus demersus) is the only penguin species that breeds on the African continent and it is currently classified as endangered. Its conservation is assisted by the Southern African Foundation for the Conservation of Coastal Birds (SANCCOB) which is a seabird rehabilitation facility based at the Rietvlei Wetland Reserve in Tableview, Cape Town. Despite the success of SANCCOB in rehabilitating diseased, injured or oiled penguins, significant mortalities have occurred at the facility as a result of avian malaria. Avian malaria can be contracted during rehabilitation during which penguins are inadvertently exposed to additional threats. An enzyme-linked immunosorbent assay (ELISA) was used to assess the anti-Plasmodium antibody levels of penguins to avian malaria on entry into the SANCCOB facility from 2001 to 2004 and during their rehabilitation process. Using blood smear data, avian malaria prevalence and malaria-related deaths were also monitored from 2002 to 2013. Significant increases in anti-Plasmodium antibody levels after admission were found during summer months. New infection and not parasite recrudescence was concluded to be the cause of this increase. This source was confirmed by a dramatic drop in penguin mortalities upon exclusion of mosquito vectors in 2008. Mortalities did not depend on the birds’ abilities to produce an anti-Plasmodium antibody response and oiling had no influence on immunity or prevalence of avian malaria infections. This study highlights the importance of mosquito vector control to control pathogen exposure in wild bird rehabilitation centres.

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Monoclonal antibodies identify the protective antigens of sporozoites of Plasmodium knowlesi.

Cited by 87 publications

References 13 publications

A Linear Peptide Containing Minimal T- and B-Cell Epitopes ofPlasmodium falciparumCircumsporozoite Protein Elicits Protection against Transgenic Sporozoite Challenge

A Linear Peptide Containing Minimal T- and B-Cell Epitopes ofPlasmodium falciparumCircumsporozoite Protein Elicits Protection against Transgenic Sporozoite Challenge

Circumsporozoite proteins of malaria parasites contain a single immunodominant region with two or more identical epitopes.

Conservation implications of avian malaria exposure for African penguins during rehabilitation

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