Efficacy of Human Monoclonal Antibodies Against H5N1
Bs Huỳnh Đỗ Phi Thông Tin

dear Bác Trần Mạnh Ngô
Thomas Gluck, MD, a german MD, made a summary and comment of the article in Journal Watch Infectious Diseases
The authors of the original article are Simmons, ... Lanzavecchia, Subbarao
I think that you can publish the abstract by Simmons CP et al with this reference:
Simmons CP et al. PLoS Med 2007 May 29; 4: e178
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Huỳnh Đỗ Phi, M.D., MPH

dear colleagues health professionals
Efficacy of Human Monoclonal Antibodies Against H5N1 Influenza Monoclonal antibodies generated from B cells of patients who had survived H5N1 influenza were efficacious in preventing and treating H5N1 infection in a mouse model. Although currently circulating H5N1 viruses are not efficiently transmitted from person to person, H5N1 influenza remains a major global threat. New treatment strategies are urgently needed. Now, researchers (one of whom is named on a patent relating to the generation and use of human monoclonal antibodies) have generated anti-H5N1 monoclonal antibodies (mAbs) from B-cells of four Vietnamese patients who survived H5N1 infections. They selected four mAbs that demonstrated broad in vitro neutralizing activity against H5N1 and tested their prophylactic and therapeutic efficacy in BALB/c mice. These animals are highly susceptible to infection with the H5N1 viruses isolated in Asia in 1997 and since 2003.
Two mAbs were tested for pre-exposure prophylactic efficacy against an H5N1 Clade I virus isolated in Vietnam in 2004. Both conferred protection >from lethal infection, although one showed greater activity than the other. Further analysis revealed that the mAbs confer protection by limiting viral replication in the lung, attenuating virus-induced lung pathology, and blocking extrapulmonary dissemination of virus. All four mAbs provided robust protection against lethality when administered up to 72 hours after experimental infection with the H5N1 Clade I strain circulating in Vietnam in 2004; three of the four mAbs also showed therapeutic efficacy against an antigenically divergent H5N1 Clade II strain isolated in Indonesia in 2005. None of these mAbs showed activity against an H3N2 influenza virus.
Comment: Prophylaxis or treatment of H5N1 influenza with cloned human mAbs offers several advantages: It is based on antibodies of human origin, generated in response to the naturally occurring pathogen, thus improving tolerability; screening for the optimal mAb is easy; the technology is established; and large amounts of pure mAbs can be made relatively quickly. Using a cocktail of several mAbs with broad cross-reactivity against multiple epitopes of H5N1 viruses could suppress viral evasion of this form of immune therapy. Further testing of this promising concept will define the role of mAbs in our armamentarium against pandemic influenza.
Published in Journal Watch Infectious Diseases June 27, 2007
Thomas Gluck, M.D.
Prophylactic and therapeutic efficacy of human monoclonal antibodies against H5N1 influenza.
Simmons CP, Bernasconi NL, Suguitan AL, Mills K, Ward JM, Chau NV, Hien TT, Sallusto F, Ha do Q, Farrar J, de Jong MD, Lanzavecchia A, Subbarao K.
Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.

BACKGROUND: New prophylactic and therapeutic strategies to combat human infections with highly pathogenic avian influenza (HPAI) H5N1 viruses are needed. We generated neutralizing anti-H5N1 human monoclonal antibodies (mAbs) and tested their efficacy for prophylaxis and therapy in a murine model of infection.
METHODS AND FINDINGS: Using Epstein-Barr virus we immortalized memory B cells from Vietnamese adults who had recovered >from infections with HPAI H5N1 viruses. Supernatants from B cell lines were screened in a virus neutralization assay. B cell lines secreting neutralizing antibodies were cloned and the mAbs purified. The cross-reactivity of these antibodies for different strains of H5N1 was tested in vitro by neutralization assays, and their prophylactic and therapeutic efficacy in vivo was tested in mice. In vitro, mAbs FLA3.14 and FLD20.19 neutralized both Clade I and Clade II H5N1 viruses, whilst FLA5.10 and FLD21.140 neutralized Clade I viruses only. In vivo, FLA3.14 and FLA5.10 conferred protection from lethality in mice challenged with A/Vietnam/1203/04 (H5N1) in a dose-dependent manner. mAb prophylaxis provided a statistically significant reduction in pulmonary virus titer, reduced associated inflammation in the lungs, and restricted extrapulmonary dissemination of the virus. Therapeutic doses of FLA3.14, FLA5.10, FLD20.19, and FLD21.140 provided robust protection from lethality at least up to 72 h postinfection with A/Vietnam/1203/04 (H5N1). mAbs FLA3.14, FLD21.140 and FLD20.19, but not FLA5.10, were also therapeutically active in vivo against the Clade II virus A/Indonesia/5/2005 (H5N1).
CONCLUSIONS: These studies provide proof of concept that fully human mAbs with neutralizing activity can be rapidly generated from the peripheral blood of convalescent patients and that these mAbs are effective for the prevention and treatment of H5N1 infection in a mouse model. A panel of neutralizing, cross-reactive mAbs might be useful for prophylaxis or adjunctive treatment of human cases of H5N1 influenza.
Publication Types:
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
PMID: 17535101 [PubMed - indexed for MEDLINE]

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Huynh Do Phi, M.D., M.P.H