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Overcoming "original sin"

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Scientists studying flu vaccines have identified ways to overcome an obstacle called "original antigenic sin," which can impair immune responses to new flu strains.

Original antigenic sin (OAS) occurs when the immune system encounters one viral strain and then a related new one, but can only respond by making antibodies against the first strain, resulting in a less effective defense.

Researchers at the Emory Vaccine Center have demonstrated in experiments with mice that OAS can be overcome by using a vaccine additive or by repeated immunization with the second viral strain.

The findings could be important in vaccination of people with weaker immune systems, such as those with chronic infections, young children, or the elderly.

The influenza virus has become so widespread because it can infect a wide range of hosts, such as pigs and birds, and because its genome is flexible, says Joshy Jacob, an Emory microbiologist.

"Original antigenic sin is really a reflection of the agility of the influenza virus," he says. "OAS becomes a factor when the new circulating strain is a 'drifted' version of what came before. The old antibodies can't neutralize the new virus, and that helps the new virus survive."

Jacob and colleagues demonstrated that combining the immunization with a vaccine additive allows mice to respond better to the live virus. The adjuvant is a squalene oil-in-water emulsion. Squalene is a vaccine additive licensed in European countries since the 1990s but is not approved for use in the United States.

"It appears that the adjuvant is making the immune responses to the first viral strain broader, so that a wider range of antibody-producing cells are able to respond to the second strain," Jacob says.

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