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Antimicrobial Agents and Chemotherapy, December 2008, p. 4331-4337, Vol. 52, No. 12
0066-4804/08/$08.00+0     doi:10.1128/AAC.00506-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Therapeutic Activity of an Anti-Idiotypic Antibody-Derived Killer Peptide against Influenza A Virus Experimental Infection{triangledown}

Giorgio Conti,1 Walter Magliani,1 Stefania Conti,1 Lucia Nencioni,2 Rossella Sgarbanti,2 Anna Teresa Palamara,2 and Luciano Polonelli1*

Department of Pathology and Laboratory Medicine, Microbiology Section, University of Parma, Viale A. Gramsci 14, Parma 43100, Italy,1 Department of Public Health Sciences, Pharmaceutical Microbiology Section, University of Rome La Sapienza, P. le Aldo Moro 5, Rome 00185, Italy2

Received 17 April 2008/ Returned for modification 30 May 2008/ Accepted 19 September 2008

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 µg/ml. Moreover, KP administered intraperitoneally at a dose of 100 µg/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.


* Corresponding author. Mailing address: Department of Pathology and Laboratory Medicine, Microbiology Section, University of Parma, V. le Antonio Gramsci 14, Parma 43100, Italy. Phone: 39 0521 988877. Fax: 39 0521 993620. E-mail: luciano.polonelli{at}unipr.it

{triangledown} Published ahead of print on 29 September 2008.


Antimicrobial Agents and Chemotherapy, December 2008, p. 4331-4337, Vol. 52, No. 12
0066-4804/08/$08.00+0     doi:10.1128/AAC.00506-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.