tetano
Editor, Senior Moderator
Published ahead of print 6 June 2012, doi: 10.1128/JVI.00147-12
The effect of priming with H1N1 influenza viruses of variable antigenic distance on challenge with 2009 pandemic H1N1 virus
C.D. O'Donnell1,
A. Wright1,
L. Vogel1,
C.J. Wei2,
G.J. Nabel2 and
K. Subbarao1,#
1Laboratory of Infectious Diseases
2Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892
ABSTRACT
Compared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930's (Alaska/35), 1940's (Fort Monmouth/47), 1950's (Fort Warren/50), and 1990's (New Caledonia/99) and challenged with 2009 pH1N1 virus six weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The HA's of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic.
http://jvi.asm.org/content/early/2012/05/31/JVI.00147-12.abstract
The effect of priming with H1N1 influenza viruses of variable antigenic distance on challenge with 2009 pandemic H1N1 virus
C.D. O'Donnell1,
A. Wright1,
L. Vogel1,
C.J. Wei2,
G.J. Nabel2 and
K. Subbarao1,#
1Laboratory of Infectious Diseases
2Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892
ABSTRACT
Compared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930's (Alaska/35), 1940's (Fort Monmouth/47), 1950's (Fort Warren/50), and 1990's (New Caledonia/99) and challenged with 2009 pH1N1 virus six weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The HA's of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic.
http://jvi.asm.org/content/early/2012/05/31/JVI.00147-12.abstract