Monday, May 29, 2023

Japan MOH To Stockpile 10 Million Doses of H5N1 Vaccine

Credit Japan MOH 


Although there are no guarantees that avian H5N1 will spark the next pandemic, its recent global surge and its increasing ability to spillover into mammalian wildlife make it a credible threat.  Of course, H5N1 has loomed large before - only to recede - and that could happen again. 

Over the past 20 years we've seen many nations - including the United States - stockpile relatively small quantities of H5N1 pre-pandemic vaccines.  

Since these vaccines have a limited shelf life, and these viruses continue to evolve, it is impractical to stockpile large quantities. As new clades appear the WHO & CDC Work to Develop Candidate H5N1 Vaccinesand to date more than three dozen H5 CVVs have been selected by WHO for development.

Most of those viruses are now extinct, making this an expensive proposition, but having an already approved CVV can save weeks or even months of valuable time if mass production and distribution of a vaccine are ever required.

Since manufacturing any useful amount of vaccine - even assuming a matching CVV is already available - would take months, some countries are once again considering stockpiling a limited quantity of updated H5N1 vaccine.  

Late last week Japan's MOH announced their intention to produce and stockpile enough to vaccinate 10 million people (about 8% of their population). 

The MOH outlined their rationale for this more in the following (translated) statement:

HPAIV (H5N1) has not acquired the ability to efficiently transmit from person to person, and is unlikely to lead to a pandemic in humans at this time. Since many cases of infection with HPAIV (H5N1) have been reported, the chances of human exposure to HPAIV (H5N1) are increasing, and there is a high possibility that sporadic cases of human infection will continue to be reported.

As the infection spreads in animals, amino acid mutations accumulate and the infectivity to humans becomes higher.

We cannot deny the possibility that such viruses will emerge in the future.

Although the two documents released by the MOH (PDF 1 and PDF 2) are in Japanese, I've machine translated the summary below.

Summary image of the above correspondence

Pre-pandemic vaccine strains to be stockpiled for up to 10 million people were selected from Clade, which is widely spread and has been observed in mammals, among the H5 subtypes that have been prevalent in recent years.

Of these, in view of the vaccine production schedule, we will select vaccine strains owned by the National Institute of Infectious Diseases. On top of that, from the viewpoint of antigenic similarity with the prevalent virus strain, this year A/Astrakhan/3212/2020 (IDCDC-RG71A) will be stockpile

Regarding the selection of vaccine strains for FY2024 and beyond, we will promptly consider the latest findings, including the possibility of manufacturing by companies. In addition, based on the recent research and development of vaccines against the new coronavirus infection, we will reconsider the stockpiling policy, including future research.

The gamble being that since a fully evolved pandemic strain has not emerged, there are no guarantees the currently selected CVV will be good match.  As a result, next year Japan will re-evaluate the situation and possibly select a different CVV for future manufacturing. 

Since we've seen difficulties in producing bulk H5N1 vaccines in the past, particularly in egg-based production facilities (see Manufacturing Pandemic Flu Vaccines: Easier Said Than Done), smaller runs (without a time imperative) could help iron out manufacturing problems. 

While H5N1 has the potential to produce a deadlier pandemic than COVID, the claims on social media that it kills `50% of those who are infected' are probably overblown.  At worst, it kills 50% of those sick enough to be hospitalized, an important distinction that I go into at some length in Revisiting the H5N1 CFR (Case Fatality Rate) Debate.  

Fortunately, we have several influenza antivirals (oseltamivir, oral baloxavir, inhaled zanamivir, or intravenous peramivir) that are expected to significantly reduce morbidity and mortality from H5N1.

But having a sufficient quantity of an effective and well-tolerated vaccine would be our best protection against an H5 avian influenza.  And if we hope to have that, we need to be aggressively working towards that before a pandemic takes off.