There is an accompanying commentary

http://www.journals.uchicago.edu/JID/journal/issues/v194n2/36564/36564.html

from Dr Alan Hampson, (Australian Influenza Specialist Group, Richmond, and School of Applied Sciences and Engineering, Monash University, Clayton, Victoria, Australia) which makes the points-

"Possibly the greatest significance of Govorkova et al.´s study is the demonstration of a significant cross-strain protective effect even in the presence of minimal antibody levels. This, together with human serological data generated with an H5N3 vaccine [15], strengthens the argument for stockpiling vaccines prepared from currently available H5N1 vaccine strains. It would now be valuable to evaluate vaccines prepared under commercial-production conditions in the ferret model, particularly those that have been evaluated in human clinical trials, and to compare the protection afforded by whole-virus and split or subunit preparations. This would not only allow comparison between the human serological response and the ferret protective effect but also ensure that the results obtained in the ferret are not influenced by differences between small-scale laboratory preparations and vaccines manufactured under full good manufacturing practice conditions. Regrettably, because of the requirement for high-level biological containment, there are few facilities where such challenge experiments are possible, particularly ones that have the capacity and expertise to utilize ferrets"

I take that as a call for rigourous validation of the experimental model we might have to pin our hopes on, a call I heartily add my voice to.

People might also like to refresh their memories with a

World Health Organization Global Influenza Program Surveillance Network

paper of last October.

"Evolution of H5N1 avian influenza viruses in Asia"
Emerg Infect Dis [serial on the Internet] http://www.cdc.gov/ncidod/EID/vol11no10/05-0644.htm

It´s another (IMHO excellent as far as it goes) ferret model investigation, describing cases/strains where cross protection is not evident: "Viruses from humans and birds in clade 1, represented by VN/1203/04, were found to constitute a relatively homogeneous and distinct antigenic group characterized by poor inhibition by ferret antisera to isolates from other clades (Table 2), in particular by the ferret antiserum raised to HK/213/03 (64-fold reduction compared to the homologous titer)".

Both those strains are examined in the newly published JID paper, but strangely the work reported in the prior CDC paper is not referrred to. That´s probably because the JID paper was submitted last October, and it´s taken this long to get on our desktops.

There´s one thing referred to in the CDC paper that I would like to see explored in more detail, and haven´t found. If anyone knows of a further reference please post details here or email the flu.org.cn admin.

"VN/JPHN30321/05 showed a reduced HI titer against VN/1203/04 reference serum. This antigenic difference is correlated with 7 amino acid differences between the HA1 domain VN/1203/04 and VN/JPHN30321/05: R53K, N84D, D94N, K140R, L175M, K189R, and V219I ".

Consider: What if the eventual evolved/selected pandemic strain is like VN/JPHN30321/05, ie, that particular experiment of nature, or one like it, achieves aspirant-mode transmissability? The CDC paper´s results suggest vaccines prepared against the selected refernce strain VN/1203/04 might not be very helpful.

I´ve put up a homology scan

http://www.hotkey.net.au/~helloworld/h5n1/

which shows those amino acid differences in their native molecular context ( just add 16 to the numbers, r53K -> r69k, k140r -> k156r etc). The CDC paper doesn´t mention the k36t and d387n (cdc numbering scheme) changes that pop out in my homology scan.

Can anyone tell me why they aren´t included as correlating with antigenic differences?

Happy thinking and researching everyone,
Daniel Robertson daniel<[-_-]>helloworld.com.au