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H5N1 Antigenic Drift in Northern and Southern Vietnam

Recombinomics Commentary
March 11, 2005

>> So far, 9 viruses have been isolated from specimens
collected from southern Viet Nam.

Results show that:

(1) These viruses belong to group Z and are genetically highly similar to
the viruses isolated in 2004, including A/Vietnam/1194/2004 and
A/Vietnam/1203/2004, which are the prototype vaccine strains recommended by WHO for pandemic influenza vaccine production.

(2) Except for one virus, all the rest are antigenically closely related to
A/Vietnam/1194/2004 and A/Vietnam/1203/2004.

(3) At the receptor recognition site, there appears [to be] an avian
receptor preference.

The conclusions so far:

(1) Very little mutation has been observed since last year [2004].

(2) There is no need to change the prototype pandemic vaccine strain
selected by WHO last year [2004].

(3) Genetically, the viruses continue to show resistance to amantadine. <<

The detail provided above show that H5N1 in the south is undergoing antigenic change, which while not unexpected, is cause for concern.  Although WHO continuously announces that new isolates have not reassorted, reassortment does not change the sequence of individual genes it merely reshuffles existing genes.  The genetic change is via mutation and recombination.  This genetic change can cause antigenic drift which makes antibodies generated by infection or vaccination less effective, which is why new human vaccines are made twice a year, once for each hemisphere.

Even vaccine changes at this rate can fail to keep pace with influenza A.  This has been clear with H3N2.  After using Panama for 5 years in a row, the H3N2 vaccine component was switched to Fujian for the current season.  However, a California strain emerged in the northern hemisphere and has swept across the United States and around the world.  This emergence has correlated with clusters of student deaths and more recently nursing home deaths.  The monitoring of California -like strains is largely done by identifying reduced titers, which show that the strain is also present in southeast Asia.  The co-circulation of H5N1 and H3N2 could lead to dual infections involving H3N2 and H5N1.

However, H5N1 is clearly evolving in the absence of detection of human avian reassortants.  The host range of the virus has expanded.  More recent isolates are more likely to grow in lab animals such as mice and ferrets.  Moreover these isolates also tend to be neurotropic.  Thus, the absense of reassortants has not prevented H5N1 genetic change, which is clearly evident in one of the nine isolates mentioned above.

Since there are only nine isolates, the significance of the one that was not antigenically closely related to the pandemic prototype isolates is unknown.  These isolates would appear to be from the south, and all of the officially confirmed cases from the south have died this season.

However, there are reports of additional atypical cases that were initially said to be negative, but were positive when tested in Japan.  Retesting of these seven in Ho Chi Minh City produced 4 positives, indicating that the test in Vietnam was not run properly initially.  The repeated negative result on three however, indicated that the test lacked sensitivity.  Media reports indicated that a more sensitive test would be used in the future.  Additional media reports suggested another lab also generated negative results on these samples, which also raises questions about the sensitivity of tests being run in that lab.

Initial reports had indicated that the seven patients had recovered.  However, more recent reports indicated some of the seven had died.  Since media coverage of patients in the south abruptly stopped just before the Tet Lunar New Year on February 9, the true situation in the south is unknown.  Government announcements indicate new outbreaks in poultry in the south almost daily, bit there is no information on the cases who were hospitalized or died before the news halt.

The situation in the north is also unclear.  Thai Binh has been declared H5N1 free since February 5, and before that the number of reported poultry H5N1 in the province was relatively low.  However, geographical and familial clusters from the province have been reported and these cases clearly involve human-to-human transmission.  Recent data indicate that there has been evidence for dual infections in people in Thai Binh for over a year, which can lead to recombination and genetic instability.  The above report on the 9 isolates does not include data on the isolates from the north.  Reports indicate that northern isolates from last year were genetically distinct, even when isolated from sisters of a fatal suspect H5N1 case.

Thus, there is evidence for antigenic drift in both northern and southern Vietnam.  This change could limit the effectiveness of a pandemic vaccine.  The two H5N1 prototype isolates are virtually identical differing by just one amino acid in hemagglutinin and three amino acids in the neuraminidase. 

Thus, antigenic drift will move away from both prototypes simultaneously.

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