Impact of prior seasonal influenza vaccination and infection on pandemic A (H1N1) influenza virus replication in ferrets

Abstract

Early epidemiologic and serologic studies have suggested pre-existing immunity to the pandemic A (H1N1) 2009 influenza virus (H1N1pdm) may be altering its morbidity and mortality in humans. To determine the role that contemporary seasonal H1N1 virus infection or trivalent inactivated vaccine (TIV) might be playing in this immunity we conducted a vaccination-challenge study in ferrets. Vaccination with TIV was unable to alter subsequent morbidity or contact transmission in ferrets following challenge with H1N1pdm. Conversely, prior infection with the contemporary seasonal H1N1 strain altered morbidity, but not transmission, of H1N1pdm despite the detection of only minimal levels of cross reactive antibodies.

Figure 1

Shedding of influenza virus A/Tennessee/1-560/2009 (H1N1) in ferrets. Nasal washes were collected on days 2, 4, 7 and 9 post challenge for inoculated ferrets and on days 3, 6, and 8 post contact for naive contact animals. Virus titers were determined by end-point titration in embryonated chicken eggs. Arithmetic mean titers are given; error bars indicate standard error. The black, red, blue and yellow lines represent the titers of group 1, 2, 3, and 4 ferrets respectively. Titers of challenged ferrets are represented as solid lines and titers of their contacts are represented by dashed lines. *** refers to a statistically significant difference (Tukey's HSD: P≤0.002) between titers of group 2 inoculated ferrets and those of groups 1, 3, and 4 inoculated ferrets.

Figure 2

Weight loss of A/Tennessee/1-560/2009 inoculated ferrets. The black, red, blue and yellow curves represent the titers of groups 1, 2, 3 and 4 respectively.

Figure 3

Shedding of influenza virus A/Brisbane/59/2007 (H1N1) in ferrets. Nasal washes were collected on days 2, 4, 7 and 9 post challenge for inoculated ferrets and on days 3, 6, and 8 post contact for naive contact animals. Virus titers were determined by end-point titration in embryonated chicken eggs. Arithmetic mean titers are given; error bars indicate standard error. The red and blue lines represent the titers of groups 5 and 6 respectively. Titers of challenged ferrets are represented as solid lines and titers of their contacts are represented by dashed lines.