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Author Notes:

To whom correspondence should be addressed. E-mail: joshy.jacob@emory.edu.

Edited by Leonard A. Herzenberg, Stanford University, Stanford, CA, and approved July 10, 2012 (received for review November 4, 2009)

Author contributions: J.H.K. and J.J. designed research; J.H.K. performed research; W.G.D. and S.S. contributed new reagents/analytic tools; J.H.K., S.S., and J.J. analyzed data; and J.H.K., S.S., and J.J. wrote the paper.

Present address J.H.K.: Immunology and Pathogenesis Branch, Influenza Division, National Centers for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329.


Research Funding:

This research was supported by National Institutes of Health/National Institute of Allergy and Infectious Diseases Contract HHSN266 200700006C.


  • cross-reactivity
  • antigen presentation
  • memory T-cell activation

Strategies to alleviate original antigenic sin responses to influenza viruses


Journal Title:

Proceedings of the National Academy of Sciences


Volume 109, Number 34


, Pages 13751-13756

Type of Work:

Article | Post-print: After Peer Review


Original antigenic sin is a phenomenon wherein sequential exposure to closely related influenza virus variants reduces antibody (Ab) response to novel antigenic determinants in the second strain and, consequently, impairs the development of immune memory. This could pose a risk to the development of immune memory in persons previously infected with or vaccinated against influenza. Here, we explored strategies to overcome original antigenic sin responses in mice sequentially exposed to two closely related hemagglutinin 1 neuraminidase 1 (H1N1) influenza strains A/PR/8/34 and A/FM/1/47. We found that dendritic cell–activating adjuvants [Bordetella pertussis toxin (PT) or CpG ODN or a squalene-based oil-in-water nanoemulsion (NE)], upon administration during the second viral exposure, completely protected mice from a lethal challenge and enhanced neutralizing-Ab titers against the second virus. Interestingly, PT and NE adjuvants when administered during the first immunization even prevented original antigenic sin in subsequent immunization without any adjuvants. As an alternative to using adjuvants, we also found that repeated immunization with the second viral strain relieved the effects of original antigenic sin. Taken together, our studies provide at least three ways of overcoming original antigenic sin.

Copyright information:

Beginning with articles submitted in Volume 106 (2009) the author(s) retains copyright to individual articles, and the National Academy of Sciences of the United States of America retains an exclusive license to publish these articles and holds copyright to the collective work.

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