# 4506
For those who like their science neat and tidy, devoid of ambiguity, and rock solid . . . the following will prove less than satisfying; a discussion of OAS, or Original Antigenic Sin in this month’s EID Journal along with some valuable analysis by CIDRAP News
While fascinating, there are far more questions than answers at this point.
Original Antigenic Sin is a term coined in 1960 by Thomas Francis, Jr. in the article On the Doctrine of Original Antigenic Sin) that postulates that when the body’s immune system is exposed to and develops an immunological memory to one virus, it may be less able to mount a defense against a subsequent exposure to a second slightly different version of the virus.
Original Antigenic sin has been described in relation to influenza viruses, Dengue Fever, and HIV. You can find a terrific background piece on OAS from last year by Robert Roos in my blog entitled CIDRAP On Original Antigenic Sin
In the most recent edition of the EID Journal we get a letter suggesting OAS as an explanation for the age shift to a younger demographic we saw with novel H1N1, along with a separate commentary.
Admittedly these are confusing, often technical discussions, cloaked in more than a little uncertainty. Luckily Robert Roos, Editor of CIDRAP News, has once again stepped up with an excellent summary of this difficult concept to help us along.
No . . . you won’t find any definitive answers here, but you will find some intriguing questions.
Volume 16, Number 6–June 2010
Letter
Original Antigenic Sin and Pandemic (H1N1) 2009
Amesh A. Adalja
and D.A. Henderson
Author affiliations: University of Pittsburgh Medical Center, Baltimore, Maryland, USATo the Editor: While pandemic (H1N1) 2009 was in its earliest stages, age distribution data indicated surprisingly few cases among persons >65 years of age. The initial assumption was that few persons >65 years of age had yet to be exposed. However, as more data became available from Mexico, Australia, and the United States, the age distribution pattern persisted (1).
This observation raised the question about whether older persons were protected from infection with an influenza virus A (H1N1) strain acquired many years ago. Indeed, data from the Centers for Disease Control and Prevention showed that approximately two thirds of older persons have evidence of immunity to pandemic (H1N1) 2009 virus. In 1960, Thomas Francis proposed the hypothesis of original antigenic sin, a phenomenon whereby a person who as a child was first exposed to a specific influenza virus A would, throughout life, mount an immune response to the virus of childhood, even when exposed to other antigenically dissimilar influenza viruses. In effect, the original antibody response generated by the immune system against a specific influenza viral strain was hypothesized to have colored all future responses to influenza (2).
Volume 16, Number 6–June 2010
Commentary
The Wages of Original Antigenic Sin
David M. Morens,
What epidemiologist Thomas Francis, Jr. (1900–1969) was thinking when pondering certain inexplicable serologic data from a 1946 influenza vaccine trial may never be known. Whether in religious reverence for the beauty of science or impish delight fueled by the martini breaks of which he was so fond, Francis coined the term "original antigenic sin" to describe a curious new immunologic phenomenon. Elsewhere in this issue, Adalja and Henderson propose that original antigenic sin has altered the population age–specific incidence of infection and disease caused by influenza A pandemic (H1N1) 2009 virus and that public health responses must account for the disruption (1). What is original antigenic sin, what is its immunologic basis, and into what sort of trouble is it getting us?
Confused yet? Robert Roos of CIDRAP may not have the answers, but he does organize and explain the questions exceedingly well. Highly recommended.
Age profile of H1N1 cases sparks discussion of 'original antigenic sin'
Robert Roos
News Editor
May 28, 2010 (CIDRAP News) – A letter and commentary published this week in Emerging Infectious Diseases explore the idea that "original antigenic sin"—the hypothesis that the first influenza A virus a person encounters in childhood strongly influences his or her immune responses to all related flu viruses encountered later—may explain the partial protection that older people have against the pandemic H1N1 flu virus.
As explained in the letter by Amesh A. Adalja and D. A. Henderson of the University of Pittsburgh Medical Center, original antigenic sin (OAS) holds that a person who is exposed to an influenza A virus in childhood will, in later encounters with related flu viruses, mount an immune response primarily directed at the original virus, even when the newly encountered virus is antigenically different. An implication of the theory is that OAS can trigger an ineffective or less effective immune response when a person is exposed to a virus that's related to the original one.
Because H1N1 viruses circulated continually from 1918 until 1957, most people born before 1957 were exposed to them, Adalja and Henderson write. "According to the theory of original sin, these persons may have partial protection from severe disease from infection with the new influenza virus A (H1N1)," they state.
The accompanying commentary, written by three other experts, generally concurs that OAS may account for the protection older people enjoy but says it is unclear whether the phenomenon is a bane or a blessing overall.
Meanwhile, another virology expert told CIDRAP News that there is conflicting evidence on OAS and that it may not be necessary to invoke such a complex idea to explain older people's immunity to the pandemic virus.
