A team of researchers led by scientists at the U.S. Food and Drug Administration (FDA) generated a group of antibodies that fully protected laboratory mice from lethal doses of H1N1 viruses that cause influenza disease in people each year, as well as the H1N1 influenza virus that caused the 2009 pandemic. The antibodies also provided significant protection against the highly pathogenic (disease-causing) H5N1 influenza virus (bird flu).
The FDA scientists produced the antibodies by first infecting mice with a seasonal H1N1 influenza virus, which triggered production of antibody-producing cells. They then fused the antibody-producing cells with rapidly dividing cells called myeloma cells. The fusion of these cells produced cells called hybridomas, which acted like antibody factories, each of which released an antibody against a specific target on the influenza virus. The scientists identified the hybridoma cells that produced only antibodies against neuraminidase (NA), a protein found on the surface of influenza viruses.
Once influenza viruses enter the cells of the body, NA enables influenza viruses to be released and spread to additional cells in the respiratory tract. Therefore, antibodies that block the function of NA contribute to protection against influenza disease by preventing the spread of newly formed virus particles. Although the virus manages to escape from most of these antibodies by changing specific sites on the NA, there is evidence that anti-NA antibodies offer some continued protection against even distantly-related influenza viruses.
The finding by FDA scientists is important because they have identified conserved sites (sites that don’t change) on the NA of the seasonal H1N1 virus. This finding explains why NA-specific antibodies protect against distantly-related H1N1 and H5N1 viruses. The identification of vulnerable targets on NA that do not mutate could be used to develop a vaccine that would protect people against a broad range of influenza viruses, a universal vaccine. The antibodies might also be useful treatment for individuals infected with H5N1 or H1N1 strains of influenza viruses.
Vaccines that prevent influenza trigger production of antibodies against a different protein on the virus surface called hemagglutinin or HA. However, the targets on HA differ from one type of influenza virus to another and mutate readily. Therefore, antibodies triggered by one year’s vaccine against specific influenza vaccines might be much less potent against one or more of the viruses represented by the vaccine used in the next season. Scientists must track viruses and develop a new vaccine that triggers production of antibodies that recognize these changes each year.
A universal vaccine would not have to be modified each year to account for mutations in these viruses. The availability of such a vaccine would also enable public health officials to respond rapidly to emerging influenza viruses likely to cause epidemics and pandemics (global epidemics), such as the 2009 H1N1 influenza virus.
Scientists in FDA’s Office of Vaccines Research and Review conducted the study.
“Molecular Basis for Broad Neuraminidase Immunity: Conserved Epitopes in Seasonal and Pandemic H1N1 as well as H5N1 Influenza Viruses”
Journal of Virology
Published online ahead of print on 19 June 2013; doi:10.1128/JVI.01203-13
Hongquan Wana, Jin Gaoa, Kemin Xub, Hongjun Chenb, Laura K. Couzensa, Katie H. Riversa, Judy D. Easterbrookc, Kevin Yanga, Lei Zhongd, Mohsen Rajabia, Jianqiang Yee, Ishrat Sultanaa, Xiu-Feng Wane, Xiufan Liud, Daniel R. Perezb, Jeffery K. Taubenbergerc, Maryna C. Eichelbergera*
aDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug
Administration, Bethesda, MD 20892, USA
bDepartment of Veterinary Medicine, University of Maryland College Park and Virginia-Maryland
Regional College of Veterinary Medicine, MD 20742, USA
cViral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institutes of
Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
dAnimal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University,
Yangzhou, Jiangsu 225009, China
eDepartment of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762, USA
*Correspondence to: Maryna C. Eichelberger, PhD