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      Genetic immunization with Hantavirus vaccine combining expression of G2 glycoprotein and fused interleukin-2

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          Abstract

          In this research, we developed a novel chimeric HTNV-IL-2-G2 DNA vaccine plasmid by genetically linking IL-2 gene to the G2 segment DNA and tested whether it could be a candidate vaccine. Chimeric gene was first expressed in eukaryotic expression system pcDNA3.1 (+). The HTNV-IL-2-G2 expressed a 72 kDa fusion protein in COS-7 cells. Meanwhile, the fusion protein kept the activity of its parental proteins. Furthermore, BALB/c mice were vaccinated by the chimeric gene. ELISA, cell microculture neutralization test in vitro were used to detect the humoral immune response in immunized BALB/c mice. Lymphocyte proliferation assay was used to detect the cellular immune response.- The results showed that the chimeric gene could simultaneously evoke specific antibody against G2 glycoprotein and IL-2. And the immunized mice of every group elicited neutralizing antibodies with different titers. Lymphocyte proliferation assay results showed that the stimulation indexes of splenocytes of chimeric gene to G2 and IL-2 were significantly higher than that of other groups. Our results suggest that IL-2-based HTNV G2 DNA can induce both humoral and cellular immune response specific for HTNV G2 and can be a candidate DNA vaccine for HTNV infection.

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          Most cited references29

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          The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design.

          Interleukin-2 and interleukin-15 have pivotal roles in the control of the life and death of lymphocytes. Although their heterotrimeric receptors have two receptor subunits in common, these two cytokines have contrasting roles in adaptive immune responses. The unique role of interleukin-2 is in the elimination of self-reactive T cells to prevent autoimmunity. By contrast, interleukin-15 is dedicated to the prolonged maintenance of memory T-cell responses to invading pathogens. As discussed in this Review, the biology of these cytokines will affect the development of novel therapies for malignancy and autoimmune diseases, as well as the design of vaccines against infectious diseases.
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            Spectrum of hantavirus infection: hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome.

            Hantaviruses chronically infect rodents without apparent disease, but when they are spread by aerosolized excreta to humans, two major clinical syndromes result: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Both diseases appear to be immunopathologic, and inflammatory mediators are important in causing the clinical manifestations. In HPS, T cells act on heavily infected pulmonary endothelium, and it is suspected that gamma interferon and tumor necrosis factor are major agents of a reversible increase in vascular permeability that leads to severe, noncardiogenic pulmonary edema. HFRS has prominent systemic manifestations. The retroperitoneum is a major site of vascular leak and the kidneys suffer tubular necrosis. Both syndromes are accompanied by myocardial depression and hypotension or shock. HFRS is primarily a Eurasian disease, whereas HPS appears to be confined to the Americas; these geographic distinctions correlate with the phylogenies of the rodent hosts and the viruses that coevolved with them.
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              Active and passive vaccination against hantavirus pulmonary syndrome with Andes virus M genome segment-based DNA vaccine.

              Hantavirus pulmonary syndrome (HPS) is a rapidly progressing human disease with one of the highest case fatality rates (30 to 50%) of any acute viral disease known. There are no vaccines, effective antiviral drugs, or immunologics to prevent or treat HPS. In an attempt to develop HPS medical countermeasures, we constructed an expression plasmid, pWRG/AND-M, that contains the full-length M genome segment of Andes virus (ANDV), a South American hantavirus. Transfection experiments in cell culture indicated that both the G1 and G2 glycoproteins are expressed from pWRG/AND-M. Rhesus macaques vaccinated by gene gun with pWRG/AND-M developed remarkably high levels of neutralizing antibodies that not only neutralized ANDV but also cross-neutralized other HPS-associated hantaviruses, including Sin Nombre virus. To determine if the antibodies elicited in the monkeys could confer protection, we performed a series of passive-transfer experiments using a recently described lethal HPS animal model (i.e., adult Syrian hamsters develop HPS and die within 10 to 15 days after challenge with ANDV). When injected into hamsters 1 day before challenge, sera from the vaccinated monkeys either provided sterile protection or delayed the onset of HPS and death. When injected on day 4 or 5 after challenge, the monkey sera protected 100% of the hamsters from lethal disease. These data provide a proof of concept for a gene-based HPS vaccine and also demonstrate the potential value of a postexposure immunoprophylactic to treat individuals after exposure, or potential exposure, to these highly lethal hantaviruses.
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                Author and article information

                Journal
                Genet Vaccines Ther
                Genetic Vaccines and Therapy
                BioMed Central
                1479-0556
                2008
                22 October 2008
                : 6
                : 15
                Affiliations
                [1 ]Department of Pathogentic Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan city 430030, PR China
                [2 ]Department of Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan city 430030, PR China
                [3 ]Center of Experimental Medicine, Wuhan first hospital, Wuhan city 430022, PR China
                Article
                1479-0556-6-15
                10.1186/1479-0556-6-15
                2577087
                18940009
                28e4f076-ed21-43ff-8473-4c77b55c2cc1
                Copyright © 2008 Hao et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 May 2008
                : 22 October 2008
                Categories
                Research

                Genetics
                Genetics

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