Re: WHO. Antigenic and genetic characteristics of H5N1 viruses and candidate vaccine viruses developed for potential use in human vaccines (Feb. 2009)
Commentary
Rapid H5N1 Clade 7 Evolution in Vietnam Raises Concerns
Recombinomics Commentary 14:31
February 25, 2009
Antigenic diversity is also present within clade 7 and viruses such as A/chicken/Vietnam/NCDV-03/2008 show reduced reactivity with antisera to clade 7 reference strain A/chicken/Vietnam/NCDV-016/2008.
The above comments are from the latest WHO update on H5N1 vaccine targets and represents concerns of a rapidly evolving clade 7 in Vietnam. The basis for the concern can be seen in the antisera table, where the vaccine against 016 has a titer of 320, which drops to 40 for 03. This drop is also suggested in the phylogenetic tree at the end of the report because of the length of each clade 7 node. Thus, even though both 016 and 03 are on the same branch, the length of each branch is relatively long, representing multiple changes.
Moreover, there are even more difference between the clade 7 in Vietnam and the clade 7 in China, represented by Shanxi/2. However, Shanxi/2 was from 2006 and China has already reported a clade 7 outbreak at the end of 2008, which likely has additional changes. Moreover, the clade 7 outbreak in poultry was followed by a spike in human cases, including A/Beijing/1/2009, which was almost certainly due to clade 7. The last human case in Beijing was in 2003 and was also clade 7, and clade 7 is common in poultry in areas surrounding Beijing.
The WHO report is glaringly silent on clade 7 in China. The Jiangsu outbreak was in December and sequences were generated last year because the OIE report noted the similarity with Shanxi/2. However, the Jiangsu poultry sequences are not on the tree and the only two human sequences from China in 2009 were from an infection with clade 2.3.4 or clade 2.3.2. There is not representation or comment on the other six confirmed cases, five of which were prior to the clade 2.3.2 infection. Moreover, the Beijing case began in 2008 and the sequences were described in general terms in media reports in early 2009.
The lack of any recent clade 7 sequences from China is cause for concern, as is the rapid evolution of clade 7 in Vietnam. In Vietnam, clade 7, clade 2.3.4, and clade 1 are co-circulating, providing opportunities for co-infections which lead to reassortant and recombination. Similarly, in China clade 7, clade 2.3.4 and clade 2.3.2 are co-circulating, offer similar opportunities. In fact the clade 2.3.2 from wild birds in Hong Kong, as well as the outbreaks South Korea, Japan, and Russia is a reassortant with a clade 2.3.2 HA and clade 2.3.4 in the other seven gene segments. Recombination between the clades and sub-clades leads to rapid evolution and vaccine resistance.
Thus, in addition to limited or no cross reactivity between clade 1 or 2 with clade 7, the published data supports rapid clade 7 involvement within clade 7. Thus, the vaccine against a 2008 clade 7 isolates from Vietnam has poor cross reactivity with another 2008 clade 7 isolate from Vietnam.
This rapid evolution of clade 7 in Vietnam, coupled with the absence of data on the current clade 7 circulating in China increase pandemic concerns.
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