Immunobiological activities of nontoxic lipid A: enhancement of nonspecific resistance in combination with trehalose dimycolate against viral infection and adjuvant effects |
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| Authors: | K N Masihi W Lange W Brehmer E Ribi |
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| Affiliation: | 1. Robert Koch Institute, Federal Health Office, Berlin, F.R.G.;2. Ribi Immunochem Research Inc., Hamilton, MT, U.S.A.;1. Department of Pharmaceutical Sciences, University of Perugia, 06122 Perugia, Italy;2. Department of Medicine, University of Perugia, 06132 Perugia, Italy;3. Department of Life Sciences, Laboratory of Pharmacology and Toxicology, University of Siena, 53100 Siena, Italy;4. Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy;1. Beijing Advanced Innovation Center for Food Nutrition and Human Health; College of Food Science and Nutritional Engineering, China Agricultural University; Beijing Key Laboratory for Food Nonthermal Processing, Chinese National Engineering Research Centre for Fruit and Vegetable Processing; Key Lab of Fruit and Vegetable Processing, Ministry of Agriculture, Beijing 100083, China;2. Institute of Agricultural Products Processing, Ningbo Academy of Agricultural Sciences, Ningbo 315100, China;1. INRS-Institute Armand-Frappier, Research Laboratories in Sciences Applied to Food, Canadian Irradiation Center, 531 Blvd des Prairies, Laval, Quebec H7V 1B7, Canada;2. Department of Dietetics, Collège Montmorency, 475 Blvd de l''Avenir, Laval, Quebec H7N 5H9, Canada;1. School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China;2. Henan Key Laboratory of Targeted Therapy and Diagnosis of Tumor and Major Diseases, Henan Province, Zhengzhou 450001, China |
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| Abstract: | The ability of nontoxic monophosphoryl lipid A (MPL) to stimulate nonspecific resistance against viral infection was investigated. Mice pretreated intravenously with squalane-in-water emulsions of MPL, alone or in combination with other immunostimulants, were given an aerosol of influenza virus three weeks after the pretreatment. Complete protection against lethal influenza virus infection was conferred when MPL was combined with trehalose dimycolate (TDM). The protective activity of MPL plus TDM combination was corroborated by a significant reduction of the lung virus titers. Combination of lower doses of MPL with TDM extracted from Mycobacterium bovis, but not with that of M. phlei, induced significant resistance to influenza virus. Preparations containing MPL alone, or combined with mycobacterial cell wall skeleton or muramyl dipeptide, were not effective. The adjuvant activity of MPL on bivalent influenza subunit vaccine was also studied. The primary antibody responses to influenza A and influenza B antigens were enhanced by the addition of MPL and were higher than the vaccine associated with aluminum hydroxide. The adjuvant activity of MPL was confirmed by the elevated secondary response. High levels of circulating antibodies were still present in the MPL group when antibody titers in the controls were waning. |
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