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      Protection induced by virus-like particles containing Toxoplasma gondii microneme protein 8 against highly virulent RH strain of Toxoplasma gondii infection

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          Abstract

          Toxoplasma gondii ( T. gondii) microneme protein 8 (MIC8) represents a novel, functional distinct invasion factor. In this study, we generated virus-like particles (VLPs) targeting Toxoplasma gondii MIC8 for the first time, and investigated the protection against highly virulent RH strain of T. gondii in a mouse model. We found that VLP vaccination induced Toxoplasma gondii-specific IgG and IgG1 antibody responses in the sera. Upon challenge infection with RH strain of T. gondii tachyzoites, vaccinated mice showed a significant increase of both IgG antibodies in sera and IgA antibodies in feces compared to those before challenge, and a rapid expansion of both germinal center B cell (B220 +, GL7 +) and T cell (CD4 +, CD8 +) populations. Importantly, intranasally immunized mice showed higher neutralizing antibodies and displayed no proinflammatory cytokine IFN-γ in the spleen. Mice were completely protected from a lethal challenge infection with the highly virulent T. gondii (RH) showing no body weight loss (100% survival). Our study shows the effective protection against T. gondii infection provided by VLPs containing microneme protein 8 of T. gondii, thus indicating a potential T. gondii vaccine candidate.

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          The moving junction of apicomplexan parasites: a key structure for invasion.

          Jean-François Dubremetz, Maryse Lebrun, Sébastien Besteiro (2011)
          Most Apicomplexa are obligate intracellular parasites and many are important pathogens of human and domestic animals. For a successful cell invasion, they rely on their own motility and on a firm anchorage to their host cell, depending on the secretion of proteins and the establishment of a structure called the moving junction (MJ). The MJ moves from the apical to the posterior end of the parasite, leading to the internalization of the parasite into a parasitophorous vacuole. Based on recent data obtained in Plasmodium and Toxoplasma, an emerging model emphasizes a cooperative role of secreted parasitic proteins in building the MJ and driving this crucial invasive process. More precisely, the parasite exports the microneme protein AMA1 to its own surface and the rhoptry neck RON2 protein as a receptor inserted into the host cell together with other RON partners. Ongoing and future research will certainly help refining the model by characterizing the molecular organization within the MJ and its interactions with both host and parasite cytoskeleton for anchoring of the complex. © 2011 Blackwell Publishing Ltd.
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            Virus-like particle vaccine induces protective immunity against homologous and heterologous strains of influenza virus.

            Fu-Shi Quan, Richard W. Compans, Moo Rim Kang … (2007)
            Recurrent outbreaks of highly pathogenic avian influenza virus pose the threat of pandemic spread of lethal disease and make it a priority to develop safe and effective vaccines. Influenza virus-like particles (VLPs) have been suggested to be a promising vaccine approach. However, VLP-induced immune responses, and their roles in inducing memory immune responses and cross-protective immunity have not been investigated. In this study, we developed VLPs containing influenza virus A/PR8/34 (H1N1) hemagglutinin (HA) and matrix (M1) proteins and investigated their immunogenicity, long-term cross-protective efficacy, and effects on lung proinflammatory cytokines in mice. Intranasal immunization with VLPs containing HA induced high serum and mucosal antibody titers and neutralizing activity against PR8 and A/WSN/33 (H1N1) viruses. Mice immunized with VLPs containing HA showed little or no proinflammatory lung cytokines and were protected from a lethal challenge with mouse-adapted PR8 or WSN viruses even 5 months postimmunization. Influenza VLPs induced mucosal immunoglobulin G and cellular immune responses, which were reactivated rapidly upon virus challenge. Long-lived antibody-secreting cells were detected in the bone marrow of immunized mice. Immune sera administered intranasally were able to confer 100% protection from a lethal challenge with PR8 or WSN, which provides further evidence that anti-HA antibodies are primarily responsible for preventing infection. Taken together, these results indicate that nonreplicating influenza VLPs represent a promising strategy for the development of a safe and effective vaccine to control the spread of lethal influenza viruses.
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              Zoonotic protozoa: from land to sea.

              Ronald Fayer, Jitender Dubey, David Lindsay (2004)
              Attention to worldwide pollution of the coastal marine environment has focused primarily on toxic algal blooms and pathogenic bacteria that multiply in nutrient-rich waters. However, massive but unseen amounts of feces from humans, their pets, and their domesticated animals are discharged, dumped, or carried in runoff, bringing encysted zoonotic protozoan parasites to estuaries and coastal waters. Here, they contaminate bathing beaches, are filtered and concentrated by shellfish eaten by humans and marine mammals, and infect a wide range of marine animal hosts, resulting in morbidity and mortality to some populations. This review addresses the extent of contamination and the animals affected by three genera of important zoonotic protozoa: Giardia, Cryptosporidium and Toxoplasma.
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                Author and article information

                Contributors
                Sanjai Kumar: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 13 April 2017
                Publication date Collection: 2017
                Volume: 12
                Issue: 4
                Electronic Location Identifier: e0175644
                Affiliations
                [1 ]Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Korea
                [2 ]Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB, Canada
                [3 ]Department of Medical Zoology, Kyung Hee University School of Medicine, Seoul, Korea
                Food and Drug Administration, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: FSQ.

                • Data curation: FSQ SHL.

                • Formal analysis: FSQ SHL.

                • Funding acquisition: FSQ.

                • Investigation: SHL FSQ.

                • Methodology: FSQ SHL ARK DHL IR HJC.

                • Project administration: FSQ.

                • Resources: SHL FSQ.

                • Software: SHL FSQ.

                • Supervision: SHL FSQ.

                • Validation: FSQ.

                • Visualization: FSQ SHL.

                • Writing – original draft: SHL FSQ.

                • Writing – review & editing: FSQ IR HJC.

                Author information
                http://orcid.org/0000-0003-0419-9339
                Article
                Publisher ID: PONE-D-17-02691
                DOI: 10.1371/journal.pone.0175644
                PMC ID: 5391012
                PubMed ID: 28406951
                SO-VID: 29e3af4d-1dbf-4952-b318-d4fd1f5752bf
                Copyright © © 2017 Lee et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 20 January 2017
                Date accepted : 29 March 2017
                Page count
                Figures: 8, Tables: 0, Pages: 14
                Funding
                Funded by: the National Research Foundation of Korea
                Award ID: NRF-2014R1A2A2A01004899
                Award Recipient :
                ORCID: http://orcid.org/0000-0003-0419-9339
                Funded by: the Agri-Bio Industry Technology Development Program
                Award ID: 315030-03-1-HD020
                Award Recipient :
                ORCID: http://orcid.org/0000-0003-0419-9339
                Funded by: the Ministry of Health and Welfare, Republic of Korea
                Award ID: HI15C2928
                Award Recipient :
                ORCID: http://orcid.org/0000-0003-0419-9339
                The National Research Foundation of Korea (NRF-2014R1A2A2A01004899) to Dr. Fu-Shi Quan; the Agri-Bio Industry Technology Development Program (315030-03-1-HD020) to Dr. Fu-Shi Quan; and the Ministry of Health and Welfare, Republic of Korea (HI15C2928) to Dr. Fu-Shi Quan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Subject: Biology and Life Sciences
                Subject: Organisms
                Subject: Protozoans
                Subject: Parasitic Protozoans
                Subject: Toxoplasma
                Subject: Toxoplasma Gondii
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Immune Physiology
                Subject: Antibodies
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Immune Physiology
                Subject: Antibodies
                Subject: Biology and Life Sciences
                Subject: Immunology
                Subject: Immune System Proteins
                Subject: Antibodies
                Subject: Medicine and Health Sciences
                Subject: Immunology
                Subject: Immune System Proteins
                Subject: Antibodies
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Proteins
                Subject: Immune System Proteins
                Subject: Antibodies
                Subject: Biology and Life Sciences
                Subject: Immunology
                Subject: Immune Response
                Subject: Antibody Response
                Subject: Medicine and Health Sciences
                Subject: Immunology
                Subject: Immune Response
                Subject: Antibody Response
                Subject: Research and Analysis Methods
                Subject: Immunologic Techniques
                Subject: Immunoassays
                Subject: Enzyme-Linked Immunoassays
                Subject: Biology and Life Sciences
                Subject: Immunology
                Subject: Immune Response
                Subject: Medicine and Health Sciences
                Subject: Immunology
                Subject: Immune Response
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Immune Cells
                Subject: Antibody-Producing Cells
                Subject: B Cells
                Subject: Biology and Life Sciences
                Subject: Immunology
                Subject: Immune Cells
                Subject: Antibody-Producing Cells
                Subject: B Cells
                Subject: Medicine and Health Sciences
                Subject: Immunology
                Subject: Immune Cells
                Subject: Antibody-Producing Cells
                Subject: B Cells
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Blood Cells
                Subject: White Blood Cells
                Subject: B Cells
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Immune Cells
                Subject: White Blood Cells
                Subject: B Cells
                Subject: Biology and Life Sciences
                Subject: Immunology
                Subject: Immune Cells
                Subject: White Blood Cells
                Subject: B Cells
                Subject: Medicine and Health Sciences
                Subject: Immunology
                Subject: Immune Cells
                Subject: White Blood Cells
                Subject: B Cells
                Subject: Biology and Life Sciences
                Subject: Parasitology
                Subject: Parasite Groups
                Subject: Apicomplexa
                Subject: Tachyzoites
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Immune Physiology
                Subject: Cytokines
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Immune Physiology
                Subject: Cytokines
                Subject: Biology and Life Sciences
                Subject: Immunology
                Subject: Immune System
                Subject: Innate Immune System
                Subject: Cytokines
                Subject: Medicine and Health Sciences
                Subject: Immunology
                Subject: Immune System
                Subject: Innate Immune System
                Subject: Cytokines
                Subject: Biology and Life Sciences
                Subject: Developmental Biology
                Subject: Molecular Development
                Subject: Cytokines
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