The healthcare needs for influenza vaccines have a number of important and unusual features.

• There is an annual need for influenza re-vaccination due to antigen drift of the viral pathogen, requiring a “new” vaccine.  Typically it is a trivalent vaccine, to provide breadth of protection against the prevalent strains. Typically 1 or 2 of the components change each season.  A worldwide surveillance network monitors strain changes and this leads to WHO recommendations on the vaccine strain coverage required.  Influenza has a strong seasonal pattern of incidence, with the “season” therefore varying by location.  The time window between release of recommendations (based on the dominant strain where it is the Influenza season) to when a new vaccine is required further round the globe (ie ahead of the influenza season arriving) is around six months.  With current production being in eggs and with variable technical challenges in producing a vaccine against a new strain, manufacturers have struggled to have adequate supplies available in time.  Given the timeline to produce the new vaccine, regulatory authorities also have a particular way of managing submissions, where a dossier once approved, has only specific areas where additional data is required for each new vaccine.

• In addition to frequent strain drift events, more substantial changes can occur.  This antigen shift has the potential to lead to a pandemic, as very high numbers of people have no immunity to this new virus.  Historically, pandemics affect all the population, rather than be biased towards the vulnerable groups typically affected by seasonal ‘flu.  Morbidity rates have been high.  Of the three major pandemics in the last century, two originated from Asia and occurred through reassortment of virus in avian ‘flu, resulting in a strain which can also be transmitted to and between humans.  The third – “Spanish ‘Flu” killed around 40million people (1918-20).  All three affected 20-25% of the population.  The current concern is driven in part by the elapse time from the last pandemic, as well as concern at the high level of avian ‘flu around.  Viral replication takes place inside cells and the mechanism provides significant and rapid scope for re-assortment into a different strain – this is to the virus’ evolutionary advantage, as immunity would otherwise grow to protect against an unchanged strain.

The incidence of influenza in developed countries is around 167 million per annum, with the majority (132 million) being symptomatic.  Vaccination is predominantly targeted to at-risk groups, notably elderly and those with chronic conditions, with around 60% uptake.  The overall uptake rate varies by country in the range of 10-25% across developed countries.  Vaccine protection rates are typically around 80% and while lower in the at-risk groups, the rate of hospitalisation by the vaccinated in much lower than the un-vaccinated.

Influenza is responsible for around 36,000 deaths each year in the US.  A major consequence of influenza is pneumonia, the sixth major cause of death.

A number of therapeutics are available.  These include anti-virals and neuraminidase inhibitors, but these have limited application in the elderly and children.

The combined threats of an influenza pandemic and the potential use of influenza as a bioweapon, as well a higher awareness of the risks from seasonal influenza have led to nationally implemented plans.   The value of the influenza vaccine market has doubled over the past few years.

The key unmet vaccine needs are:

• High immunogenicity (especially in preventing illness, notably pneumonia).
• Vaccines with an improved side-effect profile to increase vaccine uptake, especially in the most at-risk groups of the elderly and children.
• More efficacious vaccines against new influenza strains arising from antigenic drift
• Ability to respond to pandemic circumstance, resulting from strain shift and cross-species infection

This presents a unique opportunity for the application of ImmBio’s vaccine platform to develop improved annual and novel pandemic influenza vaccines.