Therapeutic activity of an anti-idiotypic antibody-derived killer peptide against influenza A virus experimental infection.
The in vitro and in vivo activities of a killer decapeptide (KP) against influenza A virus is described, and the mechanisms of action are suggested. KP represents the functional internal image of a yeast killer toxin that proved to exert antimicrobial and anti-human immunodeficiency virus type 1 (HIV-1) activities. Treatment with KP demonstrated a significant inhibitory activity on the replication of two strains of influenza A virus in different cell lines, as evaluated by hemagglutination, hemadsorption, and plaque assays. The complete inhibition of virus particle production and a marked reduction of the synthesis of viral proteins (membrane protein and hemagglutinin, in particular) were observed at a KP concentration of 4 microg/ml. Moreover, KP administered intraperitoneally at a dose of 100 microg/mice once a day for 10 days to influenza A/NWS/33 (H1N1) virus-infected mice improved the survival of the animals by 40% and significantly decreased the viral titers in their lungs. Overall, KP appears to be the first anti-idiotypic antibody-derived peptide that displays inhibitory activity and that has a potential therapeutic effect against pathogenic microorganisms, HIV-1, and influenza A virus by different mechanisms of action.
Conti
Giorgio
G
Department of Pathology and Laboratory Medicine, Microbiology Section, University of Parma, V. le Antonio Gramsci 14, Parma 43100, Italy.
Magliani
Walter
W
Conti
Stefania
S
Nencioni
Lucia
L
Sgarbanti
Rossella
R
Palamara
Anna Teresa
AT
Polonelli
Luciano
L
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000998:Antiviral Agents / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000502:physiology; D055646:Killer Factors, Yeast / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014764:Viral Proteins / Q000187:drug effects / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D000888:Antibodies, Anti-Idiotypic; D000998:Antiviral Agents; D055646:Killer Factors, Yeast; D010455:Peptides; D014764:Viral Proteins; C087906:killer toxin, Pichia