Researchers characterize antibodies that block H5N1 influenza viral transmission
H5N1 avian influenza is a highly pathogenic virus that has been responsible for several outbreaks of bird flu in humans over the past decade. In previous outbreaks, the virus spread through direct contact between humans and infected birds, but was not able to spread from human to human. Recent studies in ferrets have demonstrated that mutations in the viral HA gene allow the virus to be transmitted via respiratory droplets indicate that such mutations may also make the virus transmissible between humans. In this episode, James Crowe of Vanderbilt University describes his group’s recent investigation of the ability to human H5N1 vaccines to neutralize respiratory droplet transmissible forms of the virus. Using peripheral blood mononuclear cells from vaccinated humans, Crowe and colleagues identified antibodies that recognized both wild type and respiratory droplet transmissible forms of viral HA. Structural studies were used to further characterize the motifs required for antibody recognition. These findings indicate that the polyclonal sera currently used for vaccination can neutralize respiratory droplet transmissible forms of the virus.
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Abstract
Recent studies described the experimental adaptation of influenza H5 HAs that confers respiratory droplet transmission (rdt) to influenza virus in ferrets. Acquisition of the ability to transmit via aerosol may lead to the development of a highly pathogenic pandemic H5 virus. Vaccines are predicted to play an important role in H5N1 control should the virus become readily transmissible between humans. We obtained PBMCs from patients who received an A/Vietnam/1203/2004 H5N1 subunit vaccine. Human hybridomas were then generated and characterized. We identified antibodies that bound the HA head domain and recognized both WT and rdt H5 HAs. We used a combination of structural techniques to define a mechanism of antibody recognition of an H5 HA receptor–binding site that neutralized H5N1 influenza viruses and pseudoviruses carrying the HA rdt variants that have mutations near the receptor-binding site. Incorporation or retention of this critical antigenic site should be considered in the design of novel H5 HA immunogens to protect against mammalian-adapted H5N1 mutants.
Authors
Natalie J. Thornburg, David P. Nannemann, David L. Blum, Jessica A. Belser, Terrence M. Tumpey, Shyam Deshpande, Gloria A. Fritz, Gopal Sapparapu, Jens C. Krause, Jeong Hyun Lee, Andrew B. Ward, David E. Lee, Sheng Li, Katie L. Winarski, Benjamin W. Spiller, Jens Meiler, James E. Crowe Jr.
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