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. 2010 Mar 1;398(1):109-14.
doi: 10.1016/j.virol.2009.12.003. Epub 2009 Dec 24.

Safety, immunogencity, and efficacy of a cold-adapted A/Ann Arbor/6/60 (H2N2) vaccine in mice and ferrets

Grace L Chen  1 , Elaine W Lamirande, Hong Jin, George Kemble, Kanta Subbarao
Affiliations

Safety, immunogencity, and efficacy of a cold-adapted A/Ann Arbor/6/60 (H2N2) vaccine in mice and ferrets

Grace L Chen et al. Virology. .

Abstract

We studied the attenuation, immunogenicity and efficacy of the cold-adapted A/Ann Arbor/6/60 (AA ca) (H2N2) virus in mice and ferrets to evaluate its use in the event of an H2 influenza pandemic. The AA ca virus was restricted in replication in the respiratory tract of mice and ferrets. In mice, 2 doses of vaccine elicited a >4-fold rise in hemagglutination-inhibition (HAI) titer and resulted in complete inhibition of viral replication following lethal homologous wild-type virus challenge. In ferrets, a single dose of the vaccine elicited a >4-fold rise in HAI titer and conferred complete protection against homologous wild-type virus challenge in the upper respiratory tract. In both mice and ferrets, the AA ca virus provided significant protection from challenge with heterologous H2 virus challenge in the respiratory tract. The AA ca vaccine is safe, immunogenic, and efficacious against homologous and heterologous challenge in mice and ferrets, supporting the evaluation of this vaccine in clinical trials.

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Figures

Figure 1
Figure 1. Level of replication of A/AA/6/60 viruses in the respiratory tract of mice and ferrets
A. Level of replication of AA ca and AA wt viruses in mice following i.n. inoculation with 106 TCID50 /mouse of AA wt (black bars), AA ca (white bars) or L-15 medium/ mock-immunized (gray bars) on 3 dpi. Virus titers are expressed as mean±SE log10 TCID50/gm of tissue. The dashed horizontal line indicates the lower limit of detection. * 0.01 ≤p ≤ 0.05 (by Kruskal-Wallis) B. Level of replication of AA ca and AA wt viruses in ferrets following i.n. inoculation with 107 TCID50 /ferret of AA wt (black bars) or AA ca (white bars) on 3 dpi. Virus titers are expressed as mean±SE log10TCID50/gm (NT) or EID50/gm (lung) of tissue. The dashed horizontal line indicates the lower limit of detection.
Figure 1
Figure 1. Level of replication of A/AA/6/60 viruses in the respiratory tract of mice and ferrets
A. Level of replication of AA ca and AA wt viruses in mice following i.n. inoculation with 106 TCID50 /mouse of AA wt (black bars), AA ca (white bars) or L-15 medium/ mock-immunized (gray bars) on 3 dpi. Virus titers are expressed as mean±SE log10 TCID50/gm of tissue. The dashed horizontal line indicates the lower limit of detection. * 0.01 ≤p ≤ 0.05 (by Kruskal-Wallis) B. Level of replication of AA ca and AA wt viruses in ferrets following i.n. inoculation with 107 TCID50 /ferret of AA wt (black bars) or AA ca (white bars) on 3 dpi. Virus titers are expressed as mean±SE log10TCID50/gm (NT) or EID50/gm (lung) of tissue. The dashed horizontal line indicates the lower limit of detection.
Figure 2
Figure 2. Efficacy of the A/AA/6/60 ca virus against homologous challenge in mice and ferrets
A. Level of replication of AA wt viruses in mice immunized with 1 or 2 doses 106 TCID50 /mouse of AA ca (white bars) or L-15 medium/ mock-immunized (gray bars) on day 3 post-challenge with 106 TCID50 /mouse of the AA wt virus. Virus titers are expressed as mean±SE log10 TCID50/gm of tissue. The dashed horizontal line indicates the lower limit of detection. * 0.01 ≤p ≤ 0.05 (by Kruskal-Wallis) B. Level of replication of AA wt viruses in ferrets immunized with 1 dose 107 TCID50 /ferret of AA wt (black bars), AA ca (white bars) or L-15 medium/ mock-immunized (gray bars) on day 3 post-challenge with 107 TCID50 of the AA wt virus. Virus titers are expressed as mean±SE log10TCID50/gm (NT) or EID50/gm (lung) of tissue. The dashed horizontal line indicates the lower limit of detection. * 0.01 ≤p ≤ 0.05 (by Kruskal-Wallis)
Figure 2
Figure 2. Efficacy of the A/AA/6/60 ca virus against homologous challenge in mice and ferrets
A. Level of replication of AA wt viruses in mice immunized with 1 or 2 doses 106 TCID50 /mouse of AA ca (white bars) or L-15 medium/ mock-immunized (gray bars) on day 3 post-challenge with 106 TCID50 /mouse of the AA wt virus. Virus titers are expressed as mean±SE log10 TCID50/gm of tissue. The dashed horizontal line indicates the lower limit of detection. * 0.01 ≤p ≤ 0.05 (by Kruskal-Wallis) B. Level of replication of AA wt viruses in ferrets immunized with 1 dose 107 TCID50 /ferret of AA wt (black bars), AA ca (white bars) or L-15 medium/ mock-immunized (gray bars) on day 3 post-challenge with 107 TCID50 of the AA wt virus. Virus titers are expressed as mean±SE log10TCID50/gm (NT) or EID50/gm (lung) of tissue. The dashed horizontal line indicates the lower limit of detection. * 0.01 ≤p ≤ 0.05 (by Kruskal-Wallis)
Figure 3
Figure 3. Efficacy of the A/AA/6/60 ca virus against homologous and heterologous challenge in mice and ferrets
A. Efficacy of 1 dose of 106 TCID50 /mouse of AA ca (white bars) or L-15 medium/ mock-immunized (gray bars) in protection against homologous and heterologous H2 virus challenge on day 3 post-challenge with 105 TCID50 /mouse of the wt virus. Virus titers are expressed as mean±SE log10TCID50/gm of tissue. The dashed horizontal line indicates the lower limit of detection. B. Efficacy of 1 dose of 107 TCID50 /ferret of AA ca (white bars) or L-15 medium/mock-immunized (gray bars) in protection against homologous and heterologous H2 virus challenge on day 3 post-challenge with 106 TCID50 /ferret of the wt virus. Virus titers are expressed as mean±SE log10TCID50/gm of tissue. The dashed horizontal line indicates the lower limit of detection. * 0.01 ≤p ≤ 0.05 (by Kruskal-Wallis); ** p ≤ 0.01 (by Kruskal-Wallis)
Figure 3
Figure 3. Efficacy of the A/AA/6/60 ca virus against homologous and heterologous challenge in mice and ferrets
A. Efficacy of 1 dose of 106 TCID50 /mouse of AA ca (white bars) or L-15 medium/ mock-immunized (gray bars) in protection against homologous and heterologous H2 virus challenge on day 3 post-challenge with 105 TCID50 /mouse of the wt virus. Virus titers are expressed as mean±SE log10TCID50/gm of tissue. The dashed horizontal line indicates the lower limit of detection. B. Efficacy of 1 dose of 107 TCID50 /ferret of AA ca (white bars) or L-15 medium/mock-immunized (gray bars) in protection against homologous and heterologous H2 virus challenge on day 3 post-challenge with 106 TCID50 /ferret of the wt virus. Virus titers are expressed as mean±SE log10TCID50/gm of tissue. The dashed horizontal line indicates the lower limit of detection. * 0.01 ≤p ≤ 0.05 (by Kruskal-Wallis); ** p ≤ 0.01 (by Kruskal-Wallis)
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