Monoclonal Neutralizing Antibodies Show Promise Against Avian Flu

Main Category: Bird Flu / Avian Flu
Article Date: 29 May 2007 - 12:00 PDT

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Starting with blood of patients who survived a bout of avian flu (infection with the H5N1 strain), Cameron Simmons (of the Oxford University Clinical Research Unit at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam) and colleagues generated neutralizing human monoclonal antibodies and show that they can halt viral growth in mice deliberately infected with H5N1 virus.

The researchers isolated and immortalized antibody-producing immune cells from the patients' blood and purified the antibody made by individual cells. These monoclonal antibodies were then tested for their ability to neutralize H5N1 and other flu viruses in laboratory assays. The researchers identified several antibodies that neutralized the H5N1 strain with which the patients were originally infected and chose four for further study. In the laboratory, all four antibodies neutralized closely related H5N1 viruses and two antibodies also neutralized an H5N1 virus from a different lineage (clade) that has also caused human disease.

The researchers then tested the four antibodies in mice infected with an H5N1 virus from VietNam. The antibodies protected mice when given prior to infection, and up to 72 hours after the infection. The researchers showed that the antibodies protected mice by limiting viral replication, by lessening the deleterious effects of the virus in the lungs, and by stopping viral spread out of the lungs. Three of the four antibodies studied also protected mice infected with a H5N1 virus from a different clade.

These results indicate that passive immunotherapy with human monoclonal antibodies could help to combat avian H5N1 if (or when) it starts a human pandemic. Passive immunotherapy is already used to prevent infections with several viruses. In addition, a crude form of the approach-early treatment of patients with plasma (the liquid portion of blood) from convalescent patients-halved the death rate during the Spanish flu pandemic.

Large amounts of pure monoclonal antibodies can be readily made for clinical use and, importantly, this study indicates that some monoclonal antibodies neutralize H5N1 viruses from different clades.

The researchers sound a note of caution, however. They suggest that before passive immunotherapy can help to halt an H5N1 pandemic, additional monoclonal antibodies should be made to provide doctors with a battery of neutralizing antibodies that can neutralize not only all the currently circulating H5N1 viruses but hopefully also any newly emerging pandemic versions.

Citation:
Simmons CP, Bernasconi NL, Suguitan AL, Mills K, Ward JM, et al. (2007)
Prophylactic and therapeutic efficacy of human monoclonal antibodies against H5N1 influenza
PLoS Med 4(5): e178.
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