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September 02, 2009

Antigenic and Genetic Characteristics of Swine-Origin 2009 A(H1N1) Influenza Viruses Circulating in Humans

Garten RJ, Davis CT, Russell CA, et alScience. 2009 May 22. [Epub ahead of print]
Investigators from the Centers for Disease Control and Prevention and 25 other public health agencies around the world sought to determine the genetic origin and the antigenic characteristics of the 2009 A(H1N1) influenza virus, commonly referred to as "swine flu." Specifically, they used a genetic-similarity study to determine which influenza strains previously identified had combined to produce the new A(H1N1) flu virus.Genetic sequences of 17 flu strains isolated from Mexico and 59 strains from 12 states in the United States were compared with previously isolated strains of human seasonal influenza, influenza circulating in swine populations, and influenza circulating in avian populations. Additionally, experimental assays were used to determine which vaccine preparation would be most effective for immunization to the 2009 A(H1N1) flu strain.The genetic-similarity study found that the 2009 A(H1N1) flu was derived from the combination of 4 separate strains of influenza, each circulating in swine populations, including an A(H1N1) strain that has been circulating in swine populations since around the time of the Spanish flu outbreak of 1918. In addition, genetic similarity between the strains isolated in Mexico and those isolated in the United States suggests that the 2009 swine flu was introduced into the human population as a single event and that the virus spread into the United States from Mexico on at least 5 separate occasions. Finally, the researchers determined that because of the length of time that classic swine A(H1N1) has been circulating in swine populations vs human seasonal A(H1N1), the antigenic profile of swine A(H1N1) has drifted sufficiently so that vaccines prepared for human A(H1N1) would have little or no efficacy.
Although the mortality rate of the 2009 A(H1N1) flu is much lower than originally feared, the circulation of a previously unrecognized novel H1N1 strain in humans highlights the shortcomings of current influenza surveillance efforts worldwide. Indeed, the antigenic difference between gene segments circulating in swine populations vs humans suggests the possibility that swine populations may be a reservoir for influenza strains with pandemic potential.Genetic sequencing is capable of identifying markers for antiviral resistance and may be used to make antiviral recommendations. For example, the 2009 A(H1N1) swine flu carries a marker for resistance to adamantine antivirals. Similarly, genetic-similarity studies might be useful in selecting vaccine candidates. In this case, classic swine A(H1N1) was most genetically similar to 2009 A(H1N1), and antisera derived from classic swine A(H1N1) was most reactive to 2009 A(H1N1). These results suggest an increased need for surveillance of circulating influenza strains in swine populations, allowing for early detection of emergent influenza strains, as well as rapid recommendations for antiviral treatments and vaccine formulations.

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