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Hyperimmunes & Vaccines

We are pleased to see the recent announcements suggesting several vaccines maybe available, hopefully, from March 2021. Hyperimmunes and vaccines work hand-in-glove. We require both of these treatment modalities to protect society from the ravages of a virus like COVID-19. The more prevention and treatment options available to address this pandemic, the stronger position our society will hold. Firstly, some definitions:

Hyperimmunes

Hyperimmunes transfer the antibodies from someone who has developed immunity to an infection into a recipient who does not have that immunity. Hyperimmunes provide the recipient with immediate protection. Hyperimmunes are said to provide ‘passive immunity’ as the immunity is passed onto the recipient rather than your own body developing the immunity.

Vaccines

Vaccines use an external source to stimulate our immune system to respond to an infection. It takes time for the body to achieve protection, in the case of current information available regarding Covid-19 vaccines, up to 28 days. Vaccines are designed to spur our immune system to make an immunological response and for this reason are said to provide ‘active immunity’.

Why do you need Hyperimmunes when you have a vaccine?

While an effective vaccine(s) will hopefully eventually provide the best chance of controlling the COVID-19 pandemic, it is sadly not so simple. No vaccine will be perfect, and no vaccine will provide total protection for all recipients. No vaccine will end the pandemic instantly. The first vaccines are also likely to have significant limitations about which we will gradually learn. At this stage, important unresolved issues include:

  • vaccine performance for different groups: elderly, ethnic backgrounds, medical conditions
  • duration of protection: duration of immunity, effectiveness against evolving virus strains
  • the overall balance of benefit against harms

Elderly people

There is no guarantee vaccines under development will provide significant protection for those in most need, such as people in older age groups or those with existing medical conditions whose immune systems tend to be less effective. Not all trials are specifically recruiting such participants and there is a real possibility vaccine benefits will not extend to them. In other words, a clinical trial might show “90% efficacy” as is currently being reported in the media, however in the real world the current vaccines might not actually solve the key problems we are facing e.g. in the elderly which are by far the highest risk population.

Neither vaccine to date has been shown to perform as well in older people compared to young adults. Early phase 1 and 2 trials of the Pfizer vaccine saw the vaccine perform half as well in older individuals for antibody production. Moderna’s latest human trial assessing safety and the vaccine’s ability to induce immune responses showed the shot induced significantly fewer T cells in adults over 71, particularly the type of T cells expected to be able to kill virus infected cells. It is concerning this vaccine could be potentially less effective in older people.

Controlling symptoms vs blocking transmission

Vaccines that control disease symptoms rather than stopping infectious viruses from being transmitted from person to person are valuable. But it is transmission-blocking vaccines that are most effective at rapidly reducing viral spread and have the highest chance of eliminating a pathogen from a population. At this stage it seems that the Moderna vaccine prevents COVID symptoms; only volunteers who developed symptoms in this trial were analysed. We don’t know if this vaccine can prevent further infections.

New mutations in SARS-CoV-2

Evolving mutations will make some, if not all, current vaccines less effective. Both the Pfizer and Moderna vaccines require two shots and therefore immunity is obtained to maximum effect only after the second shot.

Supply chain

It will take some time for vaccines to become available to everyone in the world. Supply chain issues are going to be a major issue for the mRNA vaccines, like the one developed by Pfizer which must be transported and stored at around -70℃. Such a vaccine will have little utility in low and middle income countries who have less developed health infrastructure. This vaccine will also be difficult to supply to many rural and remote communities all over the world – including Australia. This means other approaches may need to be found for these populations.

Not everyone can or will get vaccinated.

Although many will be prepared to chance the first vaccines, many others either cannot, or will not, despite government attempts at persuasion. Herd immunity via vaccination, which requires effective immunisation of at least two-thirds of the population, remains a long way away.

Other strategies to reduce the spread will be with us for some time

Hyperimmunes provide immediate protection. For this reason, some groups who will always need access to hyperimmunes include healthcare workers, pregnant women, travellers and vaccine non-responders. Currently for several diseases it is essential that vaccines and hyperimmunes work in tandem, for example in tetanus, hepatitis A virus, and rabies.

Hyperimmunes are a cocktail containing the antibodies the original donor produced on exposure to a particular virus. This means the recipient receives protection against all diseases the original donor was protected against.

Hyperimmunes are “updated” for any mutation by drawing plasma from a donor who has recovered from the new mutation. In the case of vaccines, it is likely a new vaccine will have to be developed to address new mutations. In the case of Covid-19 we have already seen such a mutation in Denmark.

Finally, and perhaps not so obvious, is that the advent of a vaccine is helpful in the manufacture of hyperimmunes. People who have developed immunity via a vaccine can also donate their plasma for fractionation into a hyperimmune. This increases the supply of hyperimmune plasma reducing the cost of the plasma raw material to fractionators, such as Aegros.

The Commercial Value of Hyperimmunes

Hyperimmunes generally provide the frontline defence against any new virus outbreak. Vaccines tend to provide the second line of defence, leading to control of the virus. For example, the yearly flu vaccine has allowed society to largely control the influenzas virus.

Putting this in commercial terms, existing hyperimmunes, such as tetanus, account for US$1.5b (7%) of the $19b therapeutic plasma market. or 2.5% of the $60m vaccine market. These hyperimmune market estimates were prepared before Covid-19 and provide an estimate of the steady state hyperimmune/vaccine relative market sizes. These market sizes do not allow for the value of a Covid-19 hyperimmune such as Covimmune™.

Why does Aegros believe its Covimmune™ will be successful?

Aegros has developed its Covid-19 hyperimmune called Covimmune™ to provide passive protection for frontline healthcare workers. No other hyperimmune in development is looking to protect frontline health workers using passive immunity. The Company believes it has a natural advantage in this market because:

  • First to Market. Aegros is the only organisation currently undertaking a clinical trial of a hyperimmune to provide passive immunity for frontline healthcare workers. This means Covimmune™ should be first to market in early 2021.
  • Low Cost Producer. Aegros’ HaemaFrac™ process enables the Company to produce 4 doses of Covimmune™ per litre of convalescent plasma compared to 2 using the Chon process. This makes Aegros the industry low cost producer.
  • Small Volume Producer Using the HaemaFrac™ Aegros can process as little as 20 litres, whereas the existing fractionators require 1,000 litres per batch. As Covid-19 plasma is hard to source this is a real time to market advantage for Aegros.

In short, a vaccine is positive for Aegros.