Influenza

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, such as the emergence of the new swine flu-like H1 strain in 2009, rapidly overtaking the prior dominance of H3 strains. 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 typically 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 >80% in people with good immune systems. However, protection in the at-risk groups – who most need protection - is significantly lower. The anti-body dominated response of current egg-based vaccines are often inadequate. The construction of mammalian-based facilities, whilst improving speed and certainty of supply, replicate the egg-derived product, hence does not improve protection rates. In addition, product cost of goods is higher. Studies highlight that for protection in the elderly, a more CTL-biased response is required from a vaccine
Influenza is responsible for around 36,000 deaths each year in the US. A major consequence of influenza is co-infection with 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 and pathogen resistance against them has been growing.
The key unmet vaccine needs are:

• A product producing a broad immune response, to better protect the at-risk groups.
• Ability to respond quickly, with certainty and at acceptable cost, to strain changes.

Despite the significant investment in new capacity, adjuvants and vaccines, these unmet needs remain and it is by no means certain that current developments will be successful, especially against both of the major requirements. This presents a unique opportunity for the application of ImmunoBodies technology.

ImmBio’s product, FluBioVax has three key benefits:

• Broad and Deep Protection
  The inclusion of a human antibody tail confers two major benefits, by correctly targeting antigen into normal immune presentation pathways:
• It elicits both cellular & humoral responses, especially needed for high risk groups, including the elderly.
• The antigen is appropriately divided into its constitutive peptides, including all the epitopes, which are all presented on both MHC I & II. Viral drift only alters some - not all - of the antigen’s epitopes. The vaccine therefore generates lasting protection, robust to drift & variation, as most of the epitopes remain unchanged.
• Rapidly Addresses Viral Shift and Drift
  Recombinant coupling of antigens from any strain with human antibody tail – the product construct – is rapid and reliable, irrespective of the particular strain of interest. If a significant change in the circulating strain of virus occurs, especially a shift event, which requires a new construct, ImmBio is able to generate the new product in days.
• Fast, Flexible Low Cost Production
  The construct shares characteristics with mAbs, for which manufacturing processes are well established, with successful regulatory pathways. With high yield and much lower dosing level than required for therapeutic products, the cost of production is low. FluBioVax uses a fast and flexible expression system.