Prevention of influenza pneumonitis by sialic acid-conjugated dendritic polymers

被引:104
作者
Landers, JJ [1 ]
Cao, ZY [1 ]
Lee, I [1 ]
Piehler, LT [1 ]
Myc, PP [1 ]
Myc, A [1 ]
Hamouda, T [1 ]
Galecki, AT [1 ]
Baker, JR [1 ]
机构
[1] Univ Michigan, Dept Internal Med, Div Allergy, Ctr Biol Nanotechnol, Ann Arbor, MI 48109 USA
关键词
D O I
10.1086/344316
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Influenza A viral infection begins by hemagglutinin glycoproteins on the viral envelope binding to cell membrane sialic acid (SA). Free SA monomers cannot block hemagglutinin adhesion in vivo because of toxicity. Polyvalent, generation 4 (G4) SA-conjugated polyamidoamine (PAMAM) dendrimer (G4-SA) was evaluated as a means of preventing adhesion of 3 influenza A subtypes (H1N1, H2N2, and H3N2). In hemagglutination-inhibition assays, G4-SA was found to inhibit all H3N2 and 3 of 5 H1N1 influenza subtype strains at concentrations 32-170 times lower than those of SA monomers. In contrast, G4-SA had no ability to inhibit hemagglutination with H2N2 subtypes or 2 of 5 H1N1 subtype strains. In vivo experiments showed that G4-SA completely prevented infection by a H3N2 subtype in a murine influenza pneumonitis model but was not effective in preventing pneumonitis caused by an H2N2 subtype. Polyvalent binding inhibitors have potential as antiviral therapeutics, but issues related to strain specificity must be resolved.
引用
收藏
页码:1222 / 1230
页数:9
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