Fine epitope specificity of antibodies to region II of the Plasmodiumvivax circumsporozoite protein correlates with ability to bind recombinant protein and sporozoites

Bilsborough, Janine; Baumgart, Karl; Bathurst, Ian C.; Barr, Phillip; Good, Michael F.

doi:10.1016/s0001-706x(97)00648-7

Cited by 18 publications

(22 citation statements)

References 32 publications

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“…Monoclonal antibodies directed against the repeat sequences are known to passively transfer protection against sporozoite challenge in experimental models (14,49) and inhibit sporozoite invasion in liver cell cultures (10). Furthermore, unlike in P. falciparum, where natural infection leads to an almost entirely anti-repeat response, responses to P. vivax infection have shown to induce antibody responses to nonrepeat regions as well (3,7,17,47), a phenomenon also observed in murine malaria (12). Although the precise mode of antibody-mediated immunity is not clear, opsonizing (46) and agglutinating (50) antibodies have been suggested as possible mechanisms of protection.…”

Section: Resultsmentioning

confidence: 99%

“…This region has been thought to be a part of an immunologically cryptic epitope that is not recognized in the context of the entire protein but is able to induce invasion-inhibitory antibodies when used as an immunogen (38). Sporozoite infection leads to low levels of antibodies to the C-terminal region of the molecule in very few of the exposed individuals (7,48). This has been attributed to poor availability of the epitope (8), epitope competition (45), or sequence homology to thrombospondin.…”

Section: Antigenic Characterization Of Vmp 001 (I) Recognition By Momentioning

confidence: 99%

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A Novel ChimericPlasmodium vivaxCircumsporozoite Protein Induces Biologically Functional Antibodies That Recognize both VK210 and VK247 Sporozoites

et al. 2007

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A successful vaccine against Plasmodium vivax malaria would significantly improve the health and quality of the lives of more than 1 billion people around the world. A subunit vaccine is the only option in the absence of long-term culture of P. vivax parasites. The circumsporozoite protein that covers the surface of Plasmodium sporozoites is one of the best-studied malarial antigens and the most promising vaccine in clinical trials. We report here the development of a novel "immunologically optimal" recombinant vaccine expressed in Escherichia coli that encodes a chimeric CS protein encompassing repeats from the two major alleles, VK210 and VK247. This molecule is widely recognized by sera from patients naturally exposed to P. vivax infection and induces a highly potent immune response in genetically disparate strains of mice. Antibodies from immunized animals recognize both VK210 and VK247 sporozoites. Furthermore, these antibodies appear to be protective in nature since they cause the agglutination of live sporozoites, an in vitro surrogate of sporozoite infectivity. These results strongly suggest that recombinant CS is biologically active and highly immunogenic across major histocompatibility complex strains and raises the prospect that in humans this vaccine may induce protective immune responses.Outside of sub-Saharan Africa, Plasmodium vivax is the most prevalent of all human malarias. In addition to being present in tropical and subtropical regions, the ability of the parasite to complete its mosquito cycle at temperatures as low as 15°C has also allowed it to be spread in temperate climates. A unique feature of P. vivax is that some strains are capable of causing delayed infection by remaining latent for several months in the liver before emerging into the circulation to manifest clinical symptoms. Such individuals have been known to maintain transmission of malaria in areas where it is no longer naturally transmitted (41). Although P. vivax is usually not fatal, it is responsible for ca. 50% of all malaria cases worldwide (20). The large number of clinical cases and the severe morbidity this type of malaria causes contributes to a serious economic impact in developing countries. Recently, reports of severe forms of malaria caused by P. vivax infection have begun to appear (42). However, due to the fact that the disease caused by P. vivax is less lethal than P. falciparum, investments made to develop a vaccine against this parasite are lagging far behind. There is a need for concerted efforts toward developing vaccines to control the global transmission of P. vivax infections.Malaria parasites, while developing within hepatocytes, do not cause clinical illness and therefore are ideal targets for designing vaccines to protect children and malaria-naive adults against infection. Immunization with irradiation-attenuated malaria sporozoites has long been shown to induce protection against experimental sporozoite challenge in animal models and in humans (13,25), and currently efforts are ongoing to develop go...

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Section: Resultsmentioning

confidence: 99%

Section: Antigenic Characterization Of Vmp 001 (I) Recognition By Momentioning

confidence: 99%

A Novel ChimericPlasmodium vivaxCircumsporozoite Protein Induces Biologically Functional Antibodies That Recognize both VK210 and VK247 Sporozoites

et al. 2007

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“…ICMV vaccination also generated antibodies capable of recognizing the Region I domain, which may inhibit sporozoite invasion into hepatocytes by blocking receptor-ligand interactions during parasite entry (8). In contrast, the C-terminal fragment of VMP001 and the Region II domain, which share sequence homology to endogenous thrombospondin (20), were not recognized by antibodies elicited with either vaccine, suggesting lack of activation of self-reactive B cells. Taken together, these results suggest that NP vaccination generates antibody responses that are more durable and have higher avidity than those elicited by traditional adjuvants even using 10-fold less antigen, and elicit broader humoral responses with the capacity to recognize the sporozoite domains thought to be critical in protective immunity against infection.…”

Section: Enhanced Immunogenicity Of Np-formulated Antigen Enables Dosementioning

confidence: 99%

Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand T _fh cells and promote germinal center induction

Moon

Suh

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

298

278

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For subunit vaccines, adjuvants play a key role in shaping immunological memory. Nanoparticle (NP) delivery systems for antigens and/or molecular danger signals are promising adjuvants capable of promoting both cellular and humoral immune responses, but in most cases the mechanisms of action of these materials are poorly understood. Here, we studied the immune response elicited by NPs composed of multilamellar "stapled" lipid vesicles carrying a recombinant Plasmodium vivax circumsporozoite antigen, VMP001, both entrapped in the aqueous core and anchored to the lipid bilayer surfaces. Immunization with these particles and monophosphoryl lipid A (MPLA), a US Food and Drug Administrationapproved immunostimulatory agonist for Toll-like receptor-4, promoted high-titer, high-avidity antibody responses against VMP001, lasting more than 1 y in mice at 10-fold lower doses than conventional adjuvants. Compared to soluble VMP001 mixed with MPLA, VMP001-NPs promoted broader humoral responses, targeting multiple epitopes of the protein and a more balanced Th1/Th2 cytokine profile from antigen-specific T cells. To begin to understand the underlying mechanisms, we examined components of the B-cell response and found that NPs promoted robust germinal center (GC) formation at low doses of antigen where no GC induction occurred with soluble protein immunization, and that GCs nucleated near depots of NPs accumulating in the draining lymph nodes over time. In parallel, NP vaccination enhanced the expansion of antigen-specific follicular helper T cells (T fh ), compared to vaccinations with soluble VMP001 or alum. Thus, NP vaccines may be a promising strategy to enhance the durability, breadth, and potency of humoral immunity by enhancing key elements of the B-cell response.

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“…Peptides encompassing various CSP amino acid sequences (DRADGQPAG-DRADGQPAGDR) from the P. vivax were synthesized by using Model 431A Peptide Synthesizers (Applied Biosystems, Inc., Foster City, Calif., U.S.A.). The peptides included the repeated region sequences of CSP peptide antigen, which corresponded to VK210 type (5).…”

Section: Methodsmentioning

confidence: 99%

“…To reduce the interplate discrepancies, all samples were tested with the same batch of plates. Data analysis was carried out for the dichotomous group, where the cut-off value of OD for the positive ELISA test was set at a level three times higher than the mean OD value from the healthy controls (5). Comparisons of the seroprevalences by age, sex, and regions were made using the χ 2 test.…”

Section: Methodsmentioning

confidence: 99%

Seroprevalence to the Circumsporozoite Protein Peptide Antigen of Plasmodium vivax in Korean Children

Lim

Yoon

Chang

et al. 2005

Microbiology and Immunology

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Recently, malaria re‐emerged in the Republic of Korea (ROK), but there have been only a few reports on malaria seroprevalence. For the epidemiological study in children, a total of 1,176 serum samples were obtained from children and adolescent inhabitants from the three different regions, Pajoo, the Guro district in the western part of Seoul (Guro), and Ansan, from June to September 2002, when the transmission rate was high. Anti‐circumsporozoite protein (CSP) antibody levels were assessed in samples using an indirect enzyme‐linked immunosorbent assay (ELISA) method. Among the three regions, the highest IgG seroreactivity against the CSP antigen of Plasmodium vivax was found in the children from Pajoo (8.0%), followed by the children from Guro (3.2%), and those in Ansan (0.02%) had the lowest seroreactivity. In Pajoo, the profile of antibody response showed the highest in age 9, but decreased with age towards 12 years old. We found significant correlation between the seroprevalence and annual incidence in the investigated areas, suggesting that the area‐related patterns reflected the differences of inoculation rates in children.

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Fine epitope specificity of antibodies to region II of the Plasmodiumvivax circumsporozoite protein correlates with ability to bind recombinant protein and sporozoites

Cited by 18 publications

References 32 publications

A Novel ChimericPlasmodium vivaxCircumsporozoite Protein Induces Biologically Functional Antibodies That Recognize both VK210 and VK247 Sporozoites

A Novel ChimericPlasmodium vivaxCircumsporozoite Protein Induces Biologically Functional Antibodies That Recognize both VK210 and VK247 Sporozoites

Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand T _fh cells and promote germinal center induction

Seroprevalence to the Circumsporozoite Protein Peptide Antigen of Plasmodium vivax in Korean Children

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Fine epitope specificity of antibodies to region II of the Plasmodiumvivax circumsporozoite protein correlates with ability to bind recombinant protein and sporozoites

Cited by 18 publications

References 32 publications

A Novel ChimericPlasmodium vivaxCircumsporozoite Protein Induces Biologically Functional Antibodies That Recognize both VK210 and VK247 Sporozoites

A Novel ChimericPlasmodium vivaxCircumsporozoite Protein Induces Biologically Functional Antibodies That Recognize both VK210 and VK247 Sporozoites

Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand T fh cells and promote germinal center induction

Seroprevalence to the Circumsporozoite Protein Peptide Antigen of Plasmodium vivax in Korean Children

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Product

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Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand T _fh cells and promote germinal center induction