Genetic variants emerging as predominant H1N1 strains

**Barr IG. Euro Surveill. 2010;15:pii=19692.**

Certain 2009 pandemic influenza A (H1N1) strains with genetic mutations emerged as the predominant viruses circulating in Australia, New Zealand and Singapore during their 2010 influenza seasons, according to recent data.

Although H1N1 has remained genetically similar to the earliest detected viruses, A/California/7/2009, D222G and E291K mutations along the hemagglutinin gene appeared in late 2009 and were found among viruses circulating in Singapore and Australia during early 2010.

In April, an influenza A (H1N1) strain, A/Singapore/CC01/2010, also exhibited an N142D hemagglutinin mutation and M15I and N189S mutations along the neuraminidase gene. By mid-2010, viruses with these mutations became predominant in Singapore.

Influenza viruses sampled from Australia in January and February, however, mostly had the E391K mutation. Viruses with a dual E391K and N142D hemagglutinin mutation, including A/Brisbane/10/2010, also surfaced in April and were also found in the North and South Islands of New Zealand. By June, influenza viruses with these hemagglutinin and neuraminidase mutations were the most common in the region.

To examine the significance of these mutations, researchers from Australia and Singapore created a structural homology model of hemagglutinin from the A/Brisbane/10/2010 (H1N1) virus based on the A/California/04/2009 (H1N1) structure. They also used hemagglutination inhibition assays for further investigation.

Results indicated that samples from New Zealand often exhibited another hemagglutinin mutation, D111N, which is almost exclusively found combined with the V267A hemagglutinin mutation, according to the researchers, but these mutations have only occurred in a close temporal and geographic context (New Zealand and eastern Australia in July and August) and therefore may simply be related to founder effects.

Data also showed that M15I and N189S neuraminidase mutations were prevalent among viruses in Singapore and Australia by mid-2010.

Hemagglutination inhibition assay results using ferret antisera raised to A/California/7/2009-like viruses and viruses from the new variant group, such as A/Singapore/548/2010 and A/Brisbane10/2010, indicated no distinguishable antigenic properties from the reference and vaccine virus A/California/7/2009.

The researchers also conducted antigenic analysis using a small human serum panel (n=48) containing pre- and postvaccination sera from 24 Australians aged 18 to 59 years and 24 aged older than 60 years who received a single dose of inactivated 2010 Australian seasonal influenza vaccine — including A/California/7/2009-like pandemic influenza A (H1N1) virus, A/Perth/16/2009-like A (H3N2) virus and B/Brisbane/60/2008-like B virus.

When tested against an egg-grown A/Brisbane/20/2010 virus, the geometric mean titre in the sera of all vaccinated participants decreased by 53% compared with the geometric mean titre obtained against egg-grown wildtype A/California/7/2009 virus. The researchers said, however, no clear differences appeared between ferret sera and human postvaccination sera. These data indicate that no major antigenic differences exist in these variant viruses and they are similar to early H1N1 viruses.

“It remains to be seen whether this variant will continue to predominate for the rest of the influenza season in Oceania and in other parts of the Southern Hemisphere and then spread to the Northern Hemisphere or merely die out,” the researchers wrote. “Already this variant virus has been associated with several vaccine breakthroughs in teenagers and adults vaccinated in 2010 with monovalent pandemic influenza vaccine, as well as a number of fatal cases from whom the variant virus was isolated.”

The researchers also said viruses containing these genetic variants currently pose no threat but may prompt a need for a new vaccine sooner than expected.