Scientists modify smallpox vaccine to fight H5N1 bird flu
Updated March 02, 2009 08:22 AM
philstar.com
HONG KONG (Xinhua) -- A team of scientists from the University of Hong Kong and the United States on Sunday said they have developed a new vaccine strategy against the H5N1 bird flu virus by genetically modifying a smallpox vaccine.
The new vaccine is potentially a sound solution in case of an H5N1 bird flu pandemic, which many scientists have been worried about, said Malik Peiris, a microbiologist and bird flu research authority at the University of Hong Kong.
Peiris said that the new vaccine has proven safer in experiments on mice and that "a single vaccine dose will provide rapid protective immune responses."
It is also expected to enable fast mass production thanks to the possibility of using cell-culture methods, which could help avoid potential production bottlenecks as eggs will have to be used in the production of vaccines currently on offer.
And the existing facilities used for the production of smallpox vaccines can be used to produce the bird flu vaccines without much trouble, which can help reduce the costs, said another member of the research team, adding that alternative strategies available involving genetic engineering methods have been typically expensive.
The highly contagious H5N1 bird flu virus has infected hundreds of people around the globe over the past decade, with the death rate standing at round 60 percent.
There had been no confirmed cases of the virus spreading from human to human but scientists fear that a genetic mutation might enable it to jump from human to human someday, thereby leading to a global pandemic that could kill millions.
Many scientists have been working on the development of effective vaccines to prevent such a bird flu outbreak and the University of Hong Kong was among the leaders.
There are now vaccines for sale in the United States and eggs were essential in manufacturing the vaccines, which might lead to bottlenecks as eggs may not be readily available in large amount in the case of a bird flu pandemic.
Peiris said his team planned to optimize the efficacy of the new vaccine.
They will explore the new strategy to create a "universal influenza vaccine" that can fight a range of subtypes of the H5 strain of bird flu virus.
The study, co-authored by scientists from the US National Institutes of Health, is published on the March issue of the Journal of Immunology.
The Journal of Immunology, 2009, 182: 3063-3071.
Copyright © 2009 by The American Association of Immunologists, Inc.
doi:10.4049/jimmunol.0803467
Vaccinia Virus-Based Multivalent H5N1 Avian Influenza Vaccines Adjuvanted with IL-15 Confer Sterile Cross-Clade Protection in Mice1
Leo L. M. Poon*, Y. H. Connie Leung*, John M. Nicholls*, Pin-Yu Perera{dagger}, Jack H. Lichy{dagger}, Masafumi Yamamoto{ddagger}, Thomas A. Waldmann§, J. S. Malik Peiris2,* and Liyanage P. Perera2,§
* Department of Microbiology, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; {dagger} Veterans Affairs Medical Center, Washington D.C. 20422; {ddagger} Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Chiba, Japan; and § Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
The potential for a global influenza pandemic remains significant with epidemiologic and ecologic indicators revealing the entrenchment of the highly pathogenic avian influenza A H5N1 in both wild bird populations and domestic poultry flocks in Asia and in many African and European countries. Indisputably, the single most effective public health intervention in mitigating the devastation such a pandemic could unleash is the availability of a safe and effective vaccine that can be rapidly deployed for pre-exposure vaccination of millions of people. We have developed two vaccinia-based influenza vaccines that are molecularly adjuvanted with the immune stimulatory cytokine IL-15. The pentavalent Wyeth/IL-15/5Flu vaccine expresses the hemagglutinin, neuraminidase, and nucleoprotein derived from the H5N1 influenza virus A/Vietnam/1203/2004 and the matrix proteins M1 and M2 from the H5N1 A/CK/Indonesia/PA/2003 virus on the backbone of a currently licensed smallpox vaccine. The bivalent MVA/IL-15/HA/NA vaccine expresses only the H5 hemagglutinin and N1 neuraminidase on the modified vaccinia virus Ankara (MVA) backbone. Both vaccines induced cross-neutralizing Abs and robust cellular immune responses in vaccinated mice and conferred sterile cross-clade protection when challenged with the H5N1 virus of a different clade. In addition to having potential as a universal influenza vaccine, in the event of an impending pandemic the Wyeth/IL-15/5Flu is also readily amenable to bulk production to cover the global population. For those individuals for whom the use of the Wyeth vaccine is contraindicated, our MVA/IL-15/HA/NA offers a substitute or a prevaccine to be used in a mass vaccination campaign similar to the smallpox eradication campaigns of few decades ago.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research, National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases, NIH Contract HHSN266200700005C, and Area of Excellence Scheme of the University Grants Committee Hong Kong Grant AoE/M-12/06.
2 Address correspondence and reprint requests to Dr. Liyanage P. Perera, Metabolism Branch, Center for Cancer Research, Building 10, Room 4B40, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. E-mail address: pereral@mail.nih.gov or Dr. J. S. Malik Peiris, Department of Microbiology, University of Hong Kong, Pathology Building, Queen Mary Hospital Compound, Pokfulam, Hong Kong Special Administrative Region, China. E-mail address: malik@hkucc.hku.hk
3 Abbreviations used in this paper: HPAI, highly pathogenic avian influenza; MDCK, Madin-Darby canine kidney; MOI, multiplicity of infection; MVA, modified vaccinia virus Ankara.
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