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      r Ov-ASP-1, a recombinant secreted protein of the helminth Onchocerca volvulus, is a potent adjuvant for inducing antibodies to ovalbumin, HIV-1 polypeptide and SARS-CoV peptide antigens

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          Abstract

          We studied the adjuvanticity of recombinant Onchocerca volvulus activation associated protein-1 (r Ov-ASP-1) for ovalbumin (OVA) in mice. After a single immunization and one boost, r Ov-ASP-1 exceeded the efficacy of alum or MPL + TDM adjuvants in terms of end-point total IgG or IgG1 and IgG2a anti-OVA titres. Using the helminth-derived adjuvant, IgG isotype responses to OVA were of a mixed Th1/Th2 profile and spleen cell cytokines exclusively Th1-type. The potent adjuvanticity of r Ov-ASP-1 was confirmed in mice vaccinated with a 37-mer peptide from the S protein of SARS-CoV and an HIV-1 gp120-CD4 chimeric polypeptide antigen. Unusually for a helminth product, the r Ov-ASP-1 adjuvant augmented not only Th2 but also Th1 responses, the latter property being of potential utility in stimulating anti-viral immune responses.

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          Immune regulation by helminth parasites: cellular and molecular mechanisms.

          Immunology was founded by studying the body's response to infectious microorganisms, and yet microbial prokaryotes only tell half the story of the immune system. Eukaryotic pathogens--protozoa, helminths, fungi and ectoparasites--have all been powerful selective forces for immune evolution. Often, as with lethal protozoal parasites, the focus has been on acute infections and the inflammatory responses they evoke. Long-lived parasites such as the helminths, however, are more remarkable for their ability to downregulate host immunity, protecting themselves from elimination and minimizing severe pathology in the host.
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            The regulation of immunity to Leishmania major.

            Experimental infection with the intracellular protozoan Leishmania major constitutes a particularly versatile model for assessing the role of CD4+ subset development in the host response to infectious disease. The association of Th1 development with control of infection, and of Th2 cell development with progressive disease, has been well established. The capacity to manipulate the outcome, using distinct immunologic interventions, in both genetically resistant and susceptible mice has identified key effector cytokines that must be present during the time of initial priming of T cells in order to affect the CD4 switch phenotype. Roles for interferon-gamma (IFN-gamma), interleukin 12 (IL-12), and IL-4 in Th1 and Th2 maturation have been demonstrated, although additional undefined signals are required. Study of the genetically susceptible BALB/c mouse has shown failure to downmodulate IL-4 production in response to infection, a response that is critically associated with the failure to develop appropriate Th1 responses. Use of the murine L. major model continues to elucidate new methods for vaccine development and suggests a promising system for identification of genes that determine susceptibility to infection.
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              A novel therapeutic approach targeting articular inflammation using the filarial nematode-derived phosphorylcholine-containing glycoprotein ES-62.

              Understanding modulation of the host immune system by pathogens offers rich therapeutic potential. Parasitic filarial nematodes are often tolerated in human hosts for decades with little evidence of pathology and this appears to reflect parasite-induced suppression of host proinflammatory immune responses. Consistent with this, we have previously described a filarial nematode-derived, secreted phosphorylcholine-containing glycoprotein, ES-62, with immunomodulatory activities that are broadly anti-inflammatory in nature. We sought to evaluate the therapeutic potential of ES-62 in vitro and in vivo in an autoimmune disease model, namely, collagen-induced arthritis in DBA/1 mice. ES-62 given during collagen priming significantly reduced initiation of inflammatory arthritis. Crucially, ES-62 was also found to suppress collagen-induced arthritis severity and progression when administration was delayed until after clinically evident disease onset. Ex vivo analyses revealed that in both cases, the effects were associated with inhibition of collagen-specific pro-inflammatory/Th1 cytokine (TNF-alpha, IL-6, and IFN-gamma) release. In parallel in vitro human tissue studies, ES-62 was found to significantly suppress macrophage activation via cognate interaction with activated T cells. Finally, ES-62 suppressed LPS-induced rheumatoid arthritis synovial TNF-alpha and IL-6 production. Evolutionary pressure has promoted the generation by pathogens of diverse mechanisms enabling host immune system evasion and induction of "tolerance." ES-62 represents one such mechanism. We now provide proof of concept that parasite-derived immunomodulatory strategies offer a novel therapeutic opportunity in inflammatory arthritis.
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                Author and article information

                Contributors
                Journal
                Vaccine
                Vaccine
                Vaccine
                Elsevier Ltd.
                0264-410X
                1873-2518
                10 February 2005
                16 May 2005
                10 February 2005
                : 23
                : 26
                : 3446-3452
                Affiliations
                [a ]Laboratory of Molecular Parasitology, Lindsley F. Kimball Research Institute, The New York Blood Center, 310 East 67th Street, New York, NY 10021, USA
                [b ]Laboratory of Viral Immunology, Lindsley F. Kimball Research Institute, The New York Blood Center, 310 East 67th Street, New York, NY 10021, USA
                Author notes
                [* ]Corresponding author. Tel.: +44 2380 796 826; fax: +44 2380 798 519. angus.macdonald@ 123456hepcgen.com
                Article
                S0264-410X(05)00148-9
                10.1016/j.vaccine.2005.01.098
                7115491
                15837368
                bcf3a3e5-e1a1-4ab1-b891-4005f072b90f
                Copyright © 2005 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 31 August 2004
                : 27 December 2004
                : 5 January 2005
                Categories
                Article

                Infectious disease & Microbiology
                onchocerca volvulus activation associated protein-1 (rov-asp-1),adjuvant,th1/th2,nematode

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