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J Virol. Monoclonal antibodies against the fusion peptide of Hemagglutinin protect mice from lethal Influenza A H5N1 Infection.

Giuseppe

Emeritus
J Virol. 2008 Dec 24. [Epub ahead of print]

Monoclonal antibodies against the fusion peptide of Hemagglutinin protect mice from lethal Influenza A H5N1 Infection.

Prabhu N, Prabakaran M, Ho HT, Velumani S, Qiang J, Goutama M, Kwang J. - Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, Singapore, 117604; Tridel Biosciences International Pte Ltd, 101 Cecil Street, Singapore 069533; Department of Microbiology, Faculty of Medicine, National University of Singapore, Singapore.

The HA2 glycopolypeptide (gp) is highly conserved in all influenza A strains and it is known to play a major role in the fusion of the virus with the endosomal membrane in the 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 HA upon lethal infections with highly pathogenic avian influenza (HPAI) H5N1 virus.
We have identified a mAb 1C9 which binds to GLFGAIAGF, a part of the fusion peptide of the HA2 gp.
We evaluate the efficacy of mAb 1C9 as a therapy for influenza A virus infections.
This mAb, while inhibiting cell fusion in vitro when administered passively, protected 100% of mice from 5 MLD50 (50% mouse lethal dose) challenge with HPAI H5N1 influenza A viruses from two different clades.
Further, it caused earlier clearance of the virus from the lung.
The influenza virus load was assessed in lung samples of mice challenged after pre-treatment with mAb 1C9 (24 h prior to challenge) and 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.

PMID: 19109379 [PubMed - as supplied by publisher
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