Prior infection with classical swine H1N1 influenza viruses is associated with protective immunity to the 2009 pandemic H1N1 virus

Abstract

Background: The 2009 H1N1 pandemic emerged even though seasonal H1N1 viruses have circulated for decades. Epidemiological evidence suggested that the current seasonal vaccine did not offer significant protection from the novel pandemic, and that people over the age of 50 were less susceptible to infection.

Objectives: In a mouse challenge study with the 2009 pandemic H1N1 virus, we evaluated protective immune responses elicited by prior infection with human and swine influenza A viruses.

Results: Mice infected with A/Mexico/4108/2009 (Mex09) showed significant weight loss and 40% mortality. Prior infection with a 1976 classical swine H1N1 virus resulted in complete protection from Mex09 challenge. Prior infection with either a 2009 or a 1940 seasonal H1N1 influenza virus provided partial protection and a >100-fold reduction in viral lung titers at day 4 post-infection.

Conclusions: These findings indicate that in experimental animals recently induced immunity to 1918-derived H1N1 seasonal influenza viruses, and to a 1976 swine influenza virus, afford a degree of protection against the 2009 pandemic virus. Implications of these findings are discussed in the context of accumulating data suggesting partial protection of older persons during the 2009 pandemic.

Figure 1

Alignment of viral hemagglutinin (HA) antigenic sites. Representative human and swine H1 HA protein sequences were aligned. The four major H1 antigenic domains (C_b, C_a, S_a, and S_b) as defined by Brownlee and Fodor ¹⁰ are shown beneath the brackets. Amino acid residues (H1 open reading frame numbering, including the signal peptide) were aligned to the 1918 HA protein, and conserved residues are shown as dashes. Dashed lines separate swine lineage from human lineage HAs.

Figure 2

Weight loss of mice challenged with 2009 pandemic H1N1 virus. Mice were inoculated with 5 × 10⁴ PFU of A/Hickox/40 (H40), A/Swine/Iowa/76 (Sw76), A/Bethesda/50/2009 (NIH50), A/Bethesda/20/2009 (NIH20) or PBS (mock). After 28 days mice were challenged with 4 × 10⁵ PFU A/Mexico/4108/09 (Mex09) and daily weights were measured. Weights are presented as the mean percent at “day‐1” Mex09 challenge weight. Error bars represent standard deviations of the mean.

Figure 3

Pathology of mice challenged with 2009 pandemic H1N1 influenza virus. (A) Section from a mock‐inoculated animal challenged with the Mex09 virus. Moderate‐to‐marked acute alveolitis and bronchiolitis are seen (original magnification, ×200); (B) Section from a 2008 human H3N2 (NIH20) inoculated animal challenged with the Mex09 virus. Moderate‐to‐marked acute alveolitis and bronchiolitis are seen (original magnification, ×200); (C) Section from a 2009 human H1N1 (NIH50) inoculated animal challenged with the Mex09 virus. Mild‐to‐moderate acute alveolitis and bronchiolitis are seen (original magnification, ×200); (D) Section from a 1940 human H1N1 (Hx40) inoculated animal challenged with the Mex09 virus. Focal mild acute alveolitis and bronchiolitis are seen (original magnification, ×200); (E) Section from a Sw76 inoculated animal challenged with the Mex09 virus. No significant lung pathology is noted (original magnification, ×200); (F) Section from a Sw76 inoculated animal challenged with the Mex09 virus. Prominent lymphoid aggregates in the submucosa of the bronchial tree are noted (original magnification, ×100).