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Vaccine and Tamiflu Resistant H1N1 in Italy
Recombinomics Commentary 23:52
January 29, 2009

During last surveillance week, Parma's University detected first FIVE A/(H1N1) influenza virus isolations for this season in Italy.

From the analysis performed by NIC, ALL OF THEM WERE OSELTAMIVIR RESISTANT (IC50 value very high); while resistant to oseltamivir, these viruses remained susceptible to Zanamivir.

Corresponding clinical samples were collected at Parma, during week 03/2009, from three children and two adults respectively.

Among these patients, three received this season influenza vaccine, while none of them were treated with oseltamivir.

The above comments are from the week 4 report from Italy.  In week 3 the collection of the first five H1N1 isolates in Italy was reported.  The finding that all five were oseltamivir resistant was not a surprise, nor was the absence of oseltamivir usage in the infected patients.  However, it is worth noting that three of the five patients had been vaccinated.  This season the H1N1 component of the trivalent vaccine is A/Brisbane/59/2007, which is considered a “match” for the osletamivir resistant clade 2B which has become dominant throughout the northern hemisphere.

However, the sequences of H1N1 in the United States have evolved away from the 2007 isolate that is the vaccine target. All clade 2B isolates in the United States had acquired A193T on HA.  The polymorphism was also in the dominant sub-clade in South Africa over the summer, and was also in two large sub-clades in Japan this season.  Thus, it is likely that A193T is also in the H274Y positive H1N1 in Europe, which may contribute to the failure to protect the patients in Italy.

The emergence of A193T was evident in isolates in the United States and England which were collected in 2007, two months prior to the selection of the vaccine target for this season.  Moreover, A193T has not been in any of the H1N1 vaccine targets, although it was widespread in H1N2 isolates in 2003 and was also present in clade 2C in the 2006/2007 and 2007/2008 seasons in Asia.

The failure of H1N1 “matches” to protect against infection by oseltamivir resistant H1N1 is problematic for at risk individuals.

Moreover, the fixing of H274Y in H1N1 seasonal flu discounts the utility of Tamiflu stockpiled to control H5N1 through treatment or prophylaxis.

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