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Journal of Virology, March 2009, p. 2553-2562, Vol. 83, No. 6
0022-538X/09/$08.00+0     doi:10.1128/JVI.02165-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Monoclonal Antibodies against the Fusion Peptide of Hemagglutinin Protect Mice from Lethal Influenza A Virus H5N1 Infection {triangledown}

Nayana Prabhu,1,{dagger} Mookkan Prabakaran,1,{dagger} Hui-Ting Ho,1 Sumathy Velumani,1 Jia Qiang,1 Michael Goutama,2 and Jimmy Kwang1,3*

Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117604, Singapore,1 Tridel Biosciences International Pte. Ltd., 101 Cecil Street, Singapore 069533, Singapore,2 Department of Microbiology, Faculty of Medicine, National University of Singapore, Singapore, Singapore3

Received 14 October 2008/ Accepted 15 December 2008

The HA2 glycopolypeptide (gp) is highly conserved in all influenza A virus strains, and it is known to play a major role in the fusion of the virus with the endosomal membrane in host cells during the course of viral infection. Vaccines and therapeutics targeting this HA2 gp could induce efficient broad-spectrum immunity against influenza A virus infections. So far, there have been no studies on the possible therapeutic effects of monoclonal antibodies (MAbs), specifically against the fusion peptide of hemagglutinin (HA), upon lethal infections with highly pathogenic avian influenza (HPAI) H5N1 virus. We have identified MAb 1C9, which binds to GLFGAIAGF, a part of the fusion peptide of the HA2 gp. We evaluated the efficacy of MAb 1C9 as a therapy for influenza A virus infections. This MAb, which inhibited cell fusion in vitro when administered passively, protected 100% of mice from challenge with five 50% mouse lethal doses of HPAI H5N1 influenza A viruses from two different clades. Furthermore, it caused earlier clearance of the virus from the lung. The influenza virus load was assessed in lung samples from mice challenged after pretreatment with MAb 1C9 (24 h prior to challenge) and from mice receiving early treatment (24 h after challenge). The study shows that MAb 1C9, which is specific to the antigenically conserved fusion peptide of HA2, can contribute to the cross-clade protection of mice infected with H5N1 virus and mediate more effective recovery from infection.

* Corresponding author. Mailing address: Animal Health Biotechnology, Temasek Life Science Laboratory, 1 Research Link, National University of Singapore, Singapore, Singapore 117604. Phone: 65-68727473. Fax: 65-68727007. E-mail: kwang{at}tll.org.sg

{triangledown} Published ahead of print on 24 December 2008.

{dagger} N.P. and M.P. contributed equally to this work.

Journal of Virology, March 2009, p. 2553-2562, Vol. 83, No. 6
0022-538X/09/$08.00+0     doi:10.1128/JVI.02165-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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