Low Immunogenicity of a Plasmodium vivax Circumsporozoite Protein Epitope Bound by a Protective Monoclonal Antibody

Jones, Trevor R.; Yuan, Leo; Marwoto, Harijani A.; Gordon, Daniel M.; Wirtz, Robert A.; Hoffman, Stephen L.

doi:10.4269/ajtmh.1992.47.837

Cited by 12 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although it is not yet clear which regions of the P. vivax CSP confer antibody-mediated protection against sporozoites, several studies thus far have suggested that a humoral response against the Type I repeat is sufficient to induce protection [26], and specifically, the AGDR motif within the VK210 sequence has been identified as the target epitope of a monoclonal antibody that confers protection [27], [28]. We therefore assessed the quality of the antibody responses by measuring the avidity and epitope specificity of sera against the recombinant CSP.…”

Section: Resultsmentioning

confidence: 99%

Antigen-Displaying Lipid-Enveloped PLGA Nanoparticles as Delivery Agents for a Plasmodium vivax Malaria Vaccine

et al. 2012

View full text Add to dashboard Cite

The parasite Plasmodium vivax is the most frequent cause of malaria outside of sub-Saharan Africa, but efforts to develop viable vaccines against P. vivax so far have been inadequate. We recently developed pathogen-mimicking polymeric vaccine nanoparticles composed of the FDA-approved biodegradable polymer poly(lactide-co-glycolide) acid (PLGA) “enveloped” by a lipid membrane. In this study, we sought to determine whether this vaccine delivery platform could be applied to enhance the immune response against P. vivax sporozoites. A candidate malaria antigen, VMP001, was conjugated to the lipid membrane of the particles, and an immunostimulatory molecule, monophosphoryl lipid A (MPLA), was incorporated into the lipid membranes, creating pathogen-mimicking nanoparticle vaccines (VMP001-NPs). Vaccination with VMP001-NPs promoted germinal center formation and elicited durable antigen-specific antibodies with significantly higher titers and more balanced Th1/Th2 responses in vivo, compared with vaccines composed of soluble protein mixed with MPLA. Antibodies raised by NP vaccinations also exhibited enhanced avidity and affinity toward the domains within the circumsporozoite protein implicated in protection and were able to agglutinate live P. vivax sporozoites. These results demonstrate that these VMP001-NPs are promising vaccines candidates that may elicit protective immunity against P. vivax sporozoites.

show abstract

Section: Resultsmentioning

confidence: 99%

Antigen-Displaying Lipid-Enveloped PLGA Nanoparticles as Delivery Agents for a Plasmodium vivax Malaria Vaccine

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Several studies thus far have suggested that a humoral response against the Type I repeat in P. vivax CSP, specifically toward the AGDR motif within the VK210 sequence, may confer protective immunity against sporozoites (17)(18)(19). Thus, to evaluate the quality of the antibody response raised against VMP001, we assessed the avidity and epitope specificity of sera from immunized animals.…”

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.

300

278

View full text Add to dashboard Cite

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.

show abstract

“…Several studies using passive antibody transfers and immunizations with synthetic peptides suggest that immune response against repeats is sufficient to induce protection. A monoclonal antibody that has been mapped to a four-amino-acid motif (AGDR) within the VK210 sequence protected monkeys immunized passively with this antibody (11); however, immunization with a repeat-based vaccine (NS81V20) did not lead to high titers of antibodies to the AGDR motif (26). In another study using synthetic MAPs as vaccines, there was a positive correlation between protection and anti-AGDR titers (49).…”

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

View full text Add to dashboard Cite

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...

show abstract

Low Immunogenicity of a Plasmodium vivax Circumsporozoite Protein Epitope Bound by a Protective Monoclonal Antibody

Cited by 12 publications

References 0 publications

Antigen-Displaying Lipid-Enveloped PLGA Nanoparticles as Delivery Agents for a Plasmodium vivax Malaria Vaccine

Antigen-Displaying Lipid-Enveloped PLGA Nanoparticles as Delivery Agents for a Plasmodium vivax Malaria Vaccine

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

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

Contact Info

Product

Resources

About

Low Immunogenicity of a Plasmodium vivax Circumsporozoite Protein Epitope Bound by a Protective Monoclonal Antibody

Cited by 12 publications

References 0 publications

Antigen-Displaying Lipid-Enveloped PLGA Nanoparticles as Delivery Agents for a Plasmodium vivax Malaria Vaccine

Antigen-Displaying Lipid-Enveloped PLGA Nanoparticles as Delivery Agents for a Plasmodium vivax Malaria Vaccine

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

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

Contact Info

Product

Resources

About

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