vaccine failures and relenza shortage

Vaccine Failure In Severe H1N1 Cases
Recombinomics Commentary 15:44
March 2, 2010


The recent reports of vaccine failures in severe H1N1 cases in Europe and the United States have caused concern. Vaccine failure in general was expected because California/7 is a rare sub-clade with significant differences with the consensus sequence and there have been reports of low reactors which had a single amino acid difference with the consensus sequence.

However, the finding of frequent vaccine failures in severe cases has created additional concern. The vaccine was expected to provide some protection which would minimize severe cases. Although the vaccine against the 1918 virus offered better protection against 2009 pandemic challenge in mice, the current vaccine still offered some protection. However, the protection experiments used H1N1 from the earlier waves, and the emerging H1N1 may have additional changes, limiting the protection further.

In the fall wave, D225G/N was rare, but strongly associated with fatal cases. The finding that D225G created a low reactor led to concerns that an emerging H1N1 would have D255G/N because of selection pressure. The emergence of D225G was also seen in a 1919 isolate from London, which raised additional concerns regarding parallels with 1918/1919.

Similarly, the increases in H274Y raised concerns that cases could become more severe because of initial treatment with Tamiflu or subsequent treatment with Peramivir would have limited effect. Thus, the resistance could limit treatment options, which would become a serious problem H274Y became widespread. Production capacity for Relenza is significantly below Tamiflu levels, and there were shortages of the liquid pediatric Tamiflu in the fall outbreak, in spite of recommendations to limit Tamiflu treatment to patients with underlying conditions.

A winter/spring of 2010 outbreak would seriously strain antiviral stockpiles if a more severe / fatal H1N1 was in circulation, especially if it had H274Y. More severe cases would also strain health care delivery because these cases require ventilators and ECMO machines which are in limited supply, as are ICU beds.

Thus, a sharp increase in severe cases would significantly impact health care delivery and create more dire situations than were seen in the fall. These issues would be exacerbated by a public that was told that the pandemic was mild, over, or an epidemic. A realization that this information was false could create additional problems.

Sequence data on these severe cases in patients who had been vaccinated would be useful. The vaccine failure appears to be widespread, so generation of appropriate sequences, including those from lung from patients who failed anti-viral treatment, should be straightforward.