New influenza findings from University of Massachusetts, Medical Department described
2007 NOV 20 -- "This study describes a method for increasing the immunogenicity of influenza virus vaccines by exploiting the natural anti-Gal antibody to effectively target vaccines to antigen-presenting cells (APC). This method is based on enzymatic engineering of carbohydrate chains on virus envelope hemagglutinin to carry the alpha-Gal epitope (Gall alpha 1-3Gal beta 1-4GlcNAc-R)," scientists in the United States report. "This epitope interacts with anti-Gal, the most abundant antibody in humans (1% of immunoglobulins). Influenza virus vaccine expressing alpha-Gal epitopes is opsonized in situ by anti-Gal immunoglobulin G. The Fc portion of opsonizing anti-Gal interacts with Fc gamma receptors on APC and induces effective uptake of the vaccine virus by APC. APC internalizes the opsonized virus to transport it to draining lymph nodes for stimulation of influenza virus-specific T cells, thereby eliciting a protective immune response. The efficacy of such an influenza vaccine was demonstrated in alpha 1,3galactosyltransferase (alpha 1,3GT) knockout mice, which produce anti-Gal, using the influenza virus strain A/Puerto Rico/8/34-H1N1 (PR8). Synthesis of alpha-Gal epitopes on carbohydrate chains of PR8 virus (PR8(alpha gal)) was catalyzed by recombinant alpha 1,3GT, the glycosylation enzyme that synthesizes alpha-Gal epitopes in cells of nonprimate mammals. Mice immunized with PR8(alpha gal) displayed much higher numbers of PR8-specific CD8(+) and CD4(+) T cells (determined by intracellular cytokine staining and enzyme-linked immunospot assay) and produced anti-PR8 antibodies with much higher titers than mice immunized with PR8 lacking alpha-Gal epitopes. Mice immunized with PR8(alpha gal) also displayed a much higher level of protection than PR8 immunized mice after being challenged with lethal doses of live PR8 virus," wrote U.M. Abdelmotal and colleagues, University of Massachusetts, Medical Department. The researchers concluded: "We suggest that a similar method for increasing immunogenicity may be applicable to avian influenza vaccines." Abdelmotal and colleagues published their study in the Journal of Virology (Immunogenicity of influenza virus vaccine is increased by anti-Gal-mediated targeting to airitigen-presenting cells. Journal of Virology, 2007;81(17):9131-9141). For more information, contact U. Galili, University of Massachusetts, School Medical, Dept. of Medical, 364 Plantat St., Worcester, MA 01605, USA. Publisher contact information for the Journal of Virology is: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904, USA. Keywords: United States, Worcester, Flu, Influenza, University of Massachusetts, Medical Department. This article was prepared by Virus Weekly editors from staff and other reports. Copyright 2007, Virus Weekly via NewsRx.com.
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