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Referee comments: Referee 3

Posted by PLOS_ONE_Group on 04 Jan 2008 at 14:42 GMT

Referee 3's review:

The manuscript submitted by Baras and colleagues describes evaluation of vaccination using A/Vietnam/1194/04 (H5N1) against A/Indonesia/5/05 (H5N1) challenge in a ferret model. While limited in its scope, the data presented in this study demonstrate that ability of using the A/Vietnam/1194/04 formulation as a potential vaccine, even against drifted H5N1 viruses.

It is important to evaluate the capacity of candidate H5N1 vaccines to provide protection against both homologous and heterologous challenge. As such, the data presented in this manuscript is worthy of being in the scientific literature.

However, before publication, the following issues need to be addressed:

1. The authors comment that the ferrets are serologically naive to H5N1. Were the ferrets also seronegative against H1N1 and H3N2? This is important as there may have been some boosting of pre-existing cellular immunity due to vaccination that may contribute to heterologous protection. This should be tested and included as data not shown in the text.

2. More detail is required for figure 1 table legend such as number of animals per group, statistical analysis (if appropriate given the number of animals per group) and a reference for the plaque assay.

3. More detail is required for the tables such as the time points the data are taken from.

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N.B. These are the general comments made by the reviewer when reviewing this paper in light of which the manuscript was revised. Specific points addressed during revision of the paper are not shown.