Immune Response in macaques - 1918 flu virus

[sharon sanders]

Letter

Nature 445, 319-323 (18 January 2007) | <ABBR title="Digital Object Identifier" minmax_bound="true">doi</ABBR minmax_bound="true">:10.1038/nature05495; Received 11 September 2006; Accepted 29 November 2006
Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus


Darwyn Kobasa<SUP minmax_bound="true">1</SUP>, Steven M. Jones<SUP minmax_bound="true">2,</SUP><SUP minmax_bound="true">3</SUP>, Kyoko Shinya<SUP minmax_bound="true">5</SUP>, John C. Kash<SUP minmax_bound="true">6</SUP>, John Copps<SUP minmax_bound="true">8</SUP>, Hideki Ebihara<SUP minmax_bound="true">2,</SUP><SUP minmax_bound="true">9,</SUP><SUP minmax_bound="true">10,</SUP><SUP minmax_bound="true">11</SUP>, Yasuko Hatta<SUP minmax_bound="true">12</SUP>, Jin Hyun Kim<SUP minmax_bound="true">12</SUP>, Peter Halfmann<SUP minmax_bound="true">12</SUP>, Masato Hatta<SUP minmax_bound="true">12</SUP>, Friederike Feldmann<SUP minmax_bound="true">2</SUP>, Judie B. Alimonti<SUP minmax_bound="true">2</SUP>, Lisa Fernando<SUP minmax_bound="true">2</SUP>, Yan Li<SUP minmax_bound="true">1</SUP>, Michael G. Katze<SUP minmax_bound="true">6,</SUP><SUP minmax_bound="true">7</SUP>, Heinz Feldmann<SUP minmax_bound="true">2,</SUP><SUP minmax_bound="true">4</SUP> and Yoshihiro Kawaoka<SUP minmax_bound="true">9,</SUP><SUP minmax_bound="true">10,</SUP><SUP minmax_bound="true">11,</SUP><SUP minmax_bound="true">12</SUP>

1. <LI id=a1 minmax_bound="true">Respiratory Viruses, and, <LI id=a2 minmax_bound="true">Special Pathogens Program National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada <LI id=a3 minmax_bound="true">Department of Immunology and, <LI id=a4 minmax_bound="true">Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 3R2, Canada <LI id=a5 minmax_bound="true">The Avian Zoonosis Research Centre, Tottori University, Tottori 680-8550, Japan <LI id=a6 minmax_bound="true">Department of Microbiology, School of Medicine, and <LI id=a7 minmax_bound="true">Washington National Primate Research Center, University of Washington, Seattle, Washington 98195, USA <LI id=a8 minmax_bound="true">National Centre for Foreign Animal Diseases, Canadian Food Inspection Agency, Canadian Science Centre for Human and Animal Health, Winnipeg, Manitoba R3E 3M4, Canada <LI id=a9 minmax_bound="true">Division of Virology, Department of Microbiology and Immunology and <LI id=a10 minmax_bound="true">International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan <LI id=a11 minmax_bound="true">CREST, Japan Science and Technology Agency, Saitama 322-0012, Japan
2. Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA

Correspondence to: Yoshihiro Kawaoka<SUP minmax_bound="true">9,</SUP><SUP minmax_bound="true">10,</SUP><SUP minmax_bound="true">11,</SUP><SUP minmax_bound="true">12</SUP> Correspondence and requests for materials should be addressed to Y.K. (Email: kawaokay@svm.vetmed.wisc.edu).


Top of page The 1918 influenza pandemic was unusually severe, resulting in about 50 million deaths worldwide<SUP minmax_bound="true">1</SUP>. The 1918 virus is also highly pathogenic in mice, and studies have identified a multigenic origin of this virulent phenotype in mice<SUP minmax_bound="true">2, </SUP><SUP minmax_bound="true">3, </SUP><SUP minmax_bound="true">4</SUP>. However, these initial characterizations of the 1918 virus did not address the question of its pathogenic potential in primates. Here we demonstrate that the 1918 virus caused a highly pathogenic respiratory infection in a cynomolgus macaque model that culminated in acute respiratory distress and a fatal outcome. Furthermore, infected animals mounted an immune response, characterized by dysregulation of the antiviral response, that was insufficient for protection, indicating that atypical host innate immune responses may contribute to lethality. The ability of influenza viruses to modulate host immune responses, such as that demonstrated for the avian H5N1 influenza viruses<SUP minmax_bound="true">5</SUP>, may be a feature shared by the virulent influenza viruses.

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[sharon sanders]

Re: Immune Response in macaques - 1918 flu virus

Vaccine. 2008 Jan 24;26(4):562-72. Epub 2007 Dec 3A vaccine prepared from a non-pathogenic H5N1 avian influenza virus strain confers protective immunity against highly pathogenic avian influenza virus infection in cynomolgus macaques.

<!--AuthorList-->Itoh Y, Ozaki H, Tsuchiya H, Okamoto K, Torii R, Sakoda Y, Kawaoka Y, Ogasawara K, Kida H.
Department of Pathology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
In order to prepare for the emergence of pandemic influenza viruses, we have established an influenza virus library that contains non-pathogenic influenza A virus strains with 135 combinations of 15 hemagglutinin and 9 neuraminidase subtypes. In this study, we developed a vaccine against H5N1 highly pathogenic avian influenza (HPAI) virus infection in humans using a virus strain selected from the library. We examined its immunogenic potency using cynomolgus macaques as a primate model. Virus antigen-specific antibodies were elicited by intranasal or subcutaneous administration of inactivated whole virus particle vaccines. After challenge with an H5N1 HPAI virus isolate obtained from a Vietnamese patient, the virus was detected only on next day following inoculation in the nasal and/or tracheal swabs of vaccinated macaques that were asymptomatic. On the other hand, the viruses were isolated from nasal and tracheal swabs from non-vaccinated macaques until day 5 and day 7 after inoculation of the H5N1 HPAI virus, respectively. Although six non-vaccinated macaques developed a high body temperature, and two of them lost their appetite after HPAI virus infection, they recovered by the end of the 12-day observation period and did not show the severe symptoms that have been reported in human H5N1 virus infection cases. This demonstrates that the vaccine prepared with the non-pathogenic H5N1 virus from our influenza virus library conferred protective immunity against H5N1 HPAI virus infection to macaques.
PMID: 18164788 [PubMed - in process]

http://www.ncbi.nlm.nih.gov/pubmed/18164788?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum