R. Gourapura

The Ohio State University, Columbus, Ohio, United States

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Publications (8)6.72 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The M2e protein of influenza virus is highly conserved among strains and has been an attractive vaccine target for broad protection against different subtypes. Although M2e-based vaccine has been explored for more than two decades, the mouse model has been used almost exclusively and limited studies have been conducted in swine and chickens, the two most important species in influenza epidemiology. In this study, we utilized flexible norovirus P particle as a novel influenza vaccine platform to express M2e (M2e-PP). We tested immunogenicity and protective efficacy of M2e-PP in mouse, pig, and chicken model using different route of vaccination. In all 3 species, a single intramuscular or subcutaneous vaccination induced a detectable anti-M2e antibody response which increased significantly following booster vaccination. In contrast to mice, intranasal vaccination of M2e-PP in chicken and pig did not induce detectable IgG antibody. In mouse, both intranasal and subcutaneous vaccinations prevented clinical signs (body weight loss) and mortality, although intranasal route of vaccination outperformed subcutaneous vaccination in terms of level of protective efficacy. In chickens and swine, M2e-PP shows 1-2 log reduction in virus shedding, and intramuscular or subcutaneous vaccination using commercial oil adjuvant outperformed intranasal vaccination. We also observed that the addition of M2e protein to inactivated vaccine conferred improved protection compared to single regime vaccination suggesting a possible approach to modify traditional vaccination strategy. Also in chickens, addition of M2e vaccine enhanced the hemagglutination inhibition (HI) antibody response induced by inactivated vaccine. Our study shows clear difference in efficacy of M2e-based vaccine depending on the animal species and vaccination route.
    CRWAD, Chicago, Illinois.; 12/2014
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    ABSTRACT: Purpose: Pigs are mixing vessels for the emergence of new influenza viruses (IV). The IV conserved peptides have the potential to elicit cross-protective response, but without the potent vaccine delivery system they are poorly immunogenic. Biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticle (PLGA-NP) is a potent vaccine delivery system capable of presenting the antigens to the immune system, and also possess the adjuvant property. In this study PLGA-NP entrapped swine influenza virus(SwIV) peptides were tested in a pig vaccine challenge model. Methods: Norovirus P particle M2e chimera and conserved four SwIV peptides were entrapped in PLGA-NP by double-emulsion method. Influenza antibody free 4-5 weeks old conventional pigs were vaccinated twice at two weeks interval intranasally, and two weeks post-booster challenged with a SwIV (Sw/OH/24366/07) through intratracheal and intranasal routes; and at 7 days post-challenge euthanized and determined the immune correlates and viral load. Results: The PLGA-NP entrapped peptide vaccine received pigs had no fever in spite of comparable gross lung lesions compared to control virus-challenged animals. Interestingly, though the viral RNA copy numbers in BAL fluid was not significantly reduced in PLGA-NP vaccine group compared to control animals, the replicating infective virus was absent in NP vaccine received pigs. Immunologically, the difference in specific antibody, virus neutralizing and hemagglutination inhibition titers though higher in PLGA-NP vaccinated compared to control animals, the data was not statistically significant. But strikingly, the PLGA-NP vaccine received pigs had significantly increased frequencies of IFN-γ secreting CD3+CD4+CD8-, CD3+CD4-CD8+ and CD3+CD4+CD8+ cells in the lung mononuclear cells analyzed by flow cytometry. This data was consistent with the secretion of increased amounts of IFN-γ in the supernatant of in vitro stimulated lung mononuclear cells. Conclusions: Our data suggested that the PLGA-NP entrapped candidate SwIV peptides vaccine induced the viral epitope specific cell-mediated immune response in intranasally vaccinated pigs.
    CRWAD, Chicago, Illinois.; 12/2014
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    ABSTRACT: The M2e protein of influenza virus is highly conserved among strains and has been an attractive vaccine target for broad protection against different subtypes. Although M2e-based vaccine has been explored for more than two decades, the mouse model has been used almost exclusively and limited studies have been conducted in swine and chickens, the two most important species in influenza epidemiology. In this study, we utilized flexible norovirus P particle as a novel influenza vaccine platform to express M2e (M2e-PP). We tested immunogenicity and protective efficacy of M2e-PP in mouse, pig, and chicken model using different route of vaccination. In all 3 species, a single intramuscular or subcutaneous vaccination induced a detectable anti-M2e antibody response which increased significantly following booster vaccination. In contrast to mice, intranasal vaccination of M2e-PP in chicken and pig did not induce detectable IgG antibody. In mouse, both intranasal and subcutaneous vaccinations prevented clinical signs (body weight loss) and mortality, although intranasal route of vaccination outperformed subcutaneous vaccination in terms of level of protective efficacy. In chickens and swine, M2e-PP shows 1-2 log reduction in virus shedding, and intramuscular or subcutaneous vaccination using commercial oil adjuvant outperformed intranasal vaccination. We also observed that the addition of M2e protein to inactivated vaccine conferred improved protection compared to single regime vaccination suggesting a possible approach to modify traditional vaccination strategy. Also in chickens, addition of M2e vaccine enhanced the hemagglutination inhibition (HI) antibody response induced by inactivated vaccine. Our study shows clear difference in efficacy of M2e-based vaccine depending on the animal species and vaccination route.
    CRWAD Annual Meeting, Chicago, Illinois.; 12/2014
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    ABSTRACT: Swine influenza is widely prevalent in swine herds in North America and Europe causing enormous economic losses and a public health threat. Pigs can be infected by both avian and mammalian influenza viruses and are sources of generation of reassortant influenza viruses capable of causing pandemics in humans. Current commercial vaccines provide satisfactory immunity against homologous viruses; however, protection against heterologous viruses is not adequate. In this study, we evaluated the protective efficacy of an intranasal Poly I:C adjuvanted UV inactivated bivalent swine influenza vaccine consisting of Swine/OH/24366/07 H1N1 and Swine/CO/99 H3N2, referred as PAV, in maternal antibody positive pigs against an antigenic variant and a heterologous swine influenza virus challenge. Groups of three-week-old commercial-grade pigs were immunized intranasally with PAV or a commercial vaccine (CV) twice at 2 weeks intervals. Three weeks after the second immunization, pigs were challenged with the antigenic variant Swine/MN/08 H1N1 (MN08) and the heterologous Swine/NC/10 H1N2 (NC10) influenza virus. Antibodies in serum and respiratory tract, lung lesions, virus shedding in nasal secretions and virus load in lungs were assessed. Intranasal administration of PAV induced challenge viruses specific-hemagglutination inhibition- and IgG antibodies in the serum and IgA and IgG antibodies in the respiratory tract. Importantly, intranasal administration of PAV provided protection against the antigenic variant MN08 and the heterologous NC10 swine influenza viruses as evidenced by significant reductions in lung virus load, gross lung lesions and significantly reduced shedding of challenge viruses in nasal secretions. These results indicate that Poly I:C or its homologues may be effective as vaccine adjuvants capable of generating cross-protective immunity against antigenic variants/heterologous swine influenza viruses in pigs. Copyright © 2014. Published by Elsevier Ltd.
    Vaccine 11/2014; 33(4). DOI:10.1016/j.vaccine.2014.11.034 · 3.49 Impact Factor
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    ABSTRACT: CD1d molecules are structurally similar to MHC class I, but present lipid antigens as opposed to peptides. Here, we show that MHC class I molecules physically associate with (and regulate the functional expression of) mouse CD1d on the surface of cells. Low pH (3.0) acid stripping of MHC class I molecules resulted in increased surface expression of murine CD1d on antigen presenting cells as well as augmented CD1d-mediated antigen presentation to NKT cells. Consistent with the above results, TAP1-/- mice were found to have a higher percentage of type I NKT cells as compared to wild type mice. Moreover, bone marrow-derived dendritic cells from TAP1-/- mice showed increased antigen presentation by CD1d compared to wild type mice. Together, these results suggest that MHC class I molecules can regulate NKT cell function, in part, by masking CD1d.
    PLoS ONE 08/2013; 8(8):e72867. DOI:10.1371/journal.pone.0072867 · 3.23 Impact Factor
  • Hadi M Yassine · Chang-Won Lee · Renukaradhya Gourapura · Yehia M Saif
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    ABSTRACT: Influenza A viruses are enveloped viruses belonging to the family Orthomyxoviridae that encompasses four more genera: Influenza B, Influenza C, Isavirus and Thogotovirus. Type A viruses belong to the only genus that is highly infectious to a variety of mammalian and avian species. They are divided into subtypes based on two surface glycoproteins, the hemagglutinin (HA) and neuraminidase (NA). So far, 16 HA and 9 NA subtypes have been identified worldwide, making a possible combination of 144 subtypes between both proteins. Generally, individual viruses are host-specific, however, interspecies transmission of influenza A viruses is not uncommon. All of the HA and NA subtypes have been isolated from wild birds; however, infections in humans and other mammalian species are limited to a few subtypes. The replication of individual influenza A virus in a specific host is dependent on many factors including, viral proteins, host system and environmental conditions. In this review, the key findings that contribute to the transmission of influenza A viruses amongst different species are summarized.
    Animal Health Research Reviews 06/2010; 11(1):53-72. DOI:10.1017/S1466252310000137
  • Varun Dwivedi · Renukaradhya J. Gourapura
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    ABSTRACT: Histamine (HA) is one of the most versatile biogenic amines with multiple physiological functions in the central nervous system (CNS), the respiratory and the intestinal tract due to its ability to induce severe inflammatory reactions. More recently, a number of studies have established that besides its most obvious contribution in allergic reactions, HA also exerts more subtle regulatory functions influencing the orientation of the immune response, thus rekindling interest in this field of investigation. It can influence numerous functions of the cells involved in the regulation of immune responses and hematopoiesis of macrophages, dendritic cells, T lymphocytes, B lymphocytes and endothelial cells. All these cells express histamine receptors and also secrete histamine, which can selectively recruit major effector cells into tissue sites and affect their maturation, activation, polarization, and effector functions leading to chronic inflammation. Histamine regulates antigen-specific T-helper 1 (Th1) and T-helper 2 (Th2) cells, as well as related isotype specific antibody responses. Histamine acts through its receptor called as histamine receptor (H1-H4) subtypes, which positively interferes with the peripheral antigen tolerance induced by T-regulatory cells (Tregs) through several pathways. Natural killer T (NKT) cells are the heterogeneous population of innate immune T cells that have been attracted the attention of many researchers due to their potential to regulate immune responses to a variety of pathogens, tumors, autoimmune diseases etc. A majority of NKT cells in mice are invariant NKT (iNKT) cells and are considered to be immunoregulatory in nature, due to their ability to promptly produce both Th1 and Th2 cytokines rapidly upon activation. In this chapter, we have tried to focus on HA participation in NKT cell activation by functional tuning to ensure optimal cytokine production, which leads to the recruitment and activation of other immune cells involved in inflammatory responses mediated through eosinophils, mast cells, neutrophils, conventional T lymphocytes, dendritic cells etc.
    Biomedical Aspects of Histamine, 01/2010: pages 103-132; , ISBN: 978-90-481-9348-6
  • Renukaradhya Jayamurthy Gourapura · Masood A Khan · Marcus Vieira · Randy R Brutkiewicz
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    ABSTRACT: Natural killer T (NKT) cells are a T cell subpopulation known to possess immunoregulatory functions and recognize CD1d molecules. The majority of NKT cells express an invariant TCR [alpha] chain rearrangement and are called Type I NKT cells; all other NKT cells are Type II. In the current study, we have analyzed the roles for NKT cell subsets in the host’s innate antitumor response against the murine NS0 B-cell lymphoma model in vivo. As the NS0 cell line lacks detectable cell surface CD1d expression, murine CD1d1 cDNA or empty vector was transfected into NS0 cells to generate CD1d+ and control cell lines. In tumor-bearing mice, we found that Type I NKT cells conferred protection in a CD1d-dependent manner, whereas Type II NKT cells exhibited inhibitory activity. Pro- and anti-inflammatory cytokines secreted by splenocytes from tumor-bearing mice were predictive of tumor progression. Myeloid suppressor cells (CD11b+Gr1+) were present in larger numbers at the tumor site and in the spleen of tumor-bearing Type I NKT-deficient mice, suggesting a possible inhibition of antitumor immunosurveillance mediated by these cells. Therefore, there are distinct roles for NKT cell subsets in response to a B-cell lymphoma in vivo, pointing to potential novel targets to be exploited in the immunotherapy of blood cancers.
    American Association of Immunologists; 04/2007

Publication Stats

15 Citations
6.72 Total Impact Points

Institutions

  • 2010–2014
    • The Ohio State University
      • Ohio Agricultural Research and Development Center
      Columbus, Ohio, United States
  • 2013
    • Karolinska Institutet
      Сольна, Stockholm, Sweden