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Swallow it, sniff it or even make it at home: the future of Covid-19 vaccines

The last week has seen headlines across the world concerning both the supply and uptake of vaccines.  The AstraZeneca vaccine has been the subject of twin concerns: not enough is being produced and – in some countries – hesitancy in accepting this (or indeed any other) vaccine.  Aside from worries about exceptionally rare health hazards, the hesitancy in large part reflects anxieties about the high prevalence of short term side effects and questions about the benefits in the face of new variants.  In this post I look into the very near future and review how some exciting new approaches to vaccines could address many of the issues of supply, side effects and indeed efficacy.

What are the plusses and minuses of vaccines given by injection?

  • The short answer is that by injecting into muscle – with its good blood supply – the vaccine can rapidly be recognised by the immune system which can then start producing its response
  • Vaccines given by mouth or inhaled have to combat the body’s immediate defence mechanisms which are designed to protect us against the effects of infecting organisms in  what we eat or breath in – which then turn against the vaccines 

There are a lot of minuses with injectable vaccines summarised in the Table below:

Before Covid-19 what vaccines were given without injection?

  1. By Mouth
  • Because of the challenge that the saliva can stop vaccines working few vaccines have been given but this route
  • Many of my generation remember the Sabin vaccine for polio given on a sugar lump
  • The problem was that the vaccine was a weak form of polio and some children got sick
  • Most countries now use injectable vaccines for polio (in the UK given 5 times in childhood!)
  • The only other infections for which oral vaccines exist are those for infections of the intestines (which makes sense) and they include vaccines for:
    • Cholera
    • Typhoid
    • Rotavirus (causes severe gastro-enteritis in babies)
  • Even so most vaccines against cholera and typhoid are injections

2. By inhalation

  • Given (like Covid-19) the likelihood that flu is transmitted by inhaled droplets then logically some flu vaccines were designed to be administered in this way
  • Nasal flu vaccines have been widely used in the UK and elsewhere
  • They have been especially recommended for use in children
  • Nasal flu vaccines can be as effective as injectable vaccines but the response is not perfect (for either).
  • Indeed how protective nasal flu vaccines are in children varies by the main flu variant that year  as shown in the chart below
    • For example in 2017/18 the vaccines did not provide good enough protection

What about oral vaccines for Covid-19?  

  • I am aware of two oral vaccines now being tested in humans
  • The first is produced by a USA company (ImmunityBio)
  • It is based on a vaccine for the spike protein 
  • It is now being tested in South Africa
  • The second was announced yesterday between an Israeli Biotech company (Oramed) and the Indian pharmaceutical company (Premas) to develop a capsule for oral immunization against Covid-19 
  • Despite the press release, given the above it was not a world first!
  • What do we know about this vaccine
    • So far only tested in animals
    • In a single dose gave excellent antibody response
    • Active against multiple parts of the CoVid-19 virus (not just the spike protein) and could protect against mutations
    • A clinical study of 35 people completed recruitment in December and we await the results (though I gather that the antibody response may not be as good as the T cell response) 
    • My guess is though that the results are looking sufficiently good hence the announcement of the Israel/India tie up two days ago

My conclusion about oral vaccines?

  • Theoretically it should be possible to achieve sufficient immunity with an oral capsule.  
  • We should have a first  answer about how effective this will be in real life in say a couple of months and could possibly be available by the end of the year 

What about inhaled vaccines for Covid-a9?

  • Like with the oral vaccines there are two approaches that are being tried
  • The first is a version of the AstraZeneca vaccine and works in the same way (spike protein bolted onto a harmless virus)
  • This has only been tried in Macaque monkeys so far but did prove to produce a strong immune response
  • Infected  monkeys also had a rapid loss of the virus 
  • Testing in humans is awaited  
  • The second is a different type of vaccine to all the other Covid-19 vaccines 
  • It is based on a weakened form of the Covid-19 virus, indeed like many conventional vaccines for non-Covid disorders 
  • Because of this  it will create an immune response against all the bits of the virus and thus be more resilient to new variants
  • What is so clever (if it works) is that the weakened form of the virus was created by pulling apart the different genes in the original virus and reassembling them into something which is harmless
  • To illustrate this, UK readers above a certain age might remember a certain TV comedian!

My conclusion?

  • The inhaled version of the AstraZeneca approach looks OK so far and should be safe
  • Obviously early days but using a weakened form of the virus seems to me to be a risk that it could mutate.

Making your own vaccine at home!

  • Is this Star Wars or a genuine possibility?
  • The essence is to use 3D printing (also called additive manufacture)
  • For those of you not familiar with this amazing technological advance very briefly the steps are:
    • Develop a computer programme to build anything you want from basic ingredients
    • Allow the programme to access those ingredients and then the technology will physically make the desired object
    • The software can be downloaded and the object ‘printed’ locally
  • Although it is mainly used to build inanimate objects such as car parts, it has been used to create artificial bits of human tissue like skin, bone etc
  • The big advantage of the system is that the clever bit (the software) can be remote and provided you have the ingredients locally you can then make whatever you want where you want
  • The guy in the picture printed his own virus!
  • In theory therefore adopting the same approach one can 3D print a vaccine 
  • This is most useful for mRNA vaccines (like Pfizer’s) and a company CureVac is working on this
  • If it works then it could be of enormous benefit for vaccine supply and distribution especially to poorer parts of the world

My conclusion?

  • I won’t dismiss the concept
  • Certainly 3D printing is being used to produce vaccine administration systems (like very fine needles) which could reduce the amount of vaccine required 

Final words

  • The pace of even more novel vaccine development globally has been breath-taking over the past 12 months. 
  • We will need such advances to enhance vaccine production, vaccine acceptance and resilience to mutations

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5 replies on “Swallow it, sniff it or even make it at home: the future of Covid-19 vaccines”

Alan, thanks as ever for the fascinating post and for keeping us up to date. I did read a while ago that a process might be developed whereby a vaccine could possibly be made in freeze-dried form,. This would have obvious advantages for transport and preservation. It was clear that it was at an early stage, but I wonder if you think it could be feasible.

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Absolutely, indeed I am surprised it has not progressed with Covid vaccines. Well established for other vaccines. It dies add a complexity in delivery of course for then the vaccine has to be reconstituted locally so may not be great for mass innocualtions

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The Canadian/Israeli nasal spray ‘Enovid’ developed by Sanotize has already gained approval for use in New Zealand (and I think Israel, too) and looks particularly promising. Would you agree?

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Thanks David.

2 points:
1. Not that you were making this comparison, bu this nasal spray is not a vaccine but (if you like) the equivalent of hand gel for the nose
2. I am sure it is helpful but will not protect against access by mouth or eyes and probably only useful as an adjunct say in going to crowded events

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Great comment!
However, the main entry published in the literature is through the epithelial cells in the nasal cavity. This is the location where the spike protein has best access via ACE-2 receptors ( which are blocked by the active ingredient in eNOvid. We have invested gargle and nasal lavage for chronic sinusitis but the nasal route seems to be the best route where the RCT showed a 95% reduction in SARS-CoV-2 virus, including UK variant, after 24 hours and 99.5% in 72 hours in infected people with very high levels of the virus.

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