Giuseppe
Emeritus
[Source: Proceedings of the National Academy of Science of the United State of America, full page: (LINK). Abstract, edited.]
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Strategies to alleviate original antigenic sin responses to influenza viruses
Jin Hyang Kim<SUP>a</SUP>,<SUP>1</SUP>, William G. Davis<SUP>b</SUP>, Suryaprakash Sambhara<SUP>b</SUP>, and Joshy Jacob<SUP>a</SUP>,<SUP>2</SUP>
<SUP></SUP>
Author Affiliations: <SUP>a</SUP>Department of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Center, Emory University, Atlanta, GA 30329; and <SUP>b</SUP>Immunology and Pathogenesis Branch, Influenza Division, National Centers for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329
Edited* by Leonard A. Herzenberg, Stanford University, Stanford, CA, and approved July 10, 2012 (received for review November 4, 2009)
Abstract
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.
cross-reactivity - antigen presentation - memory T-cell activation
Footnotes
<SUP>1</SUP>Present address: Immunology and Pathogenesis Branch, Influenza Division, National Centers for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329.
<SUP>2</SUP>To whom correspondence should be addressed. E-mail: joshy.jacob@emory.edu.
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. The authors declare no conflict of interest.
*This Direct Submission article had a prearranged editor.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.0912458109/-/DCSupplemental.
-Jin Hyang Kim<SUP>a</SUP>,<SUP>1</SUP>, William G. Davis<SUP>b</SUP>, Suryaprakash Sambhara<SUP>b</SUP>, and Joshy Jacob<SUP>a</SUP>,<SUP>2</SUP>
<SUP></SUP>
Author Affiliations: <SUP>a</SUP>Department of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Center, Emory University, Atlanta, GA 30329; and <SUP>b</SUP>Immunology and Pathogenesis Branch, Influenza Division, National Centers for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329
Edited* by Leonard A. Herzenberg, Stanford University, Stanford, CA, and approved July 10, 2012 (received for review November 4, 2009)
Abstract
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.
cross-reactivity - antigen presentation - memory T-cell activation
Footnotes
<SUP>1</SUP>Present address: Immunology and Pathogenesis Branch, Influenza Division, National Centers for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329.
<SUP>2</SUP>To whom correspondence should be addressed. E-mail: joshy.jacob@emory.edu.
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. The authors declare no conflict of interest.
*This Direct Submission article had a prearranged editor.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.0912458109/-/DCSupplemental.
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