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Why we still vaccinate mostly using needles?

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jnikola
jnikola Nov 28, 2020
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Since the breakout of COVID-19 pandemics, the vaccine is the magic potion we all yearn for. At the same time, many of us are scared of needles, they hurt and damage our skin if applied often, their disposal is expensive and complex and their application requires trained professional. Does it have to be a needle? The paper from 2008 shows all kinds of other "vaccination" methods, such as:
  1. Through the skin or muscles (cutaneous, dermal, epicutaneous, epidermal, intradermal, patch, percutaneous, skin, topical, and transcutaneous)
  2. Using the needle
  3. Passive diffusion from the patch (with or without additives)
  4. Mechanical disruption (Tape, friction, shaving, brushing)
  5. Mechanical disruption using microneedles
  6. Heat disruption (heat of electrical resistance to disrupt tiny openings in the stratum corneum)
  7. Electricity disruption (electroporation, Iontophoresis)
  8. Light disruption by laser (laser-assisted drug delivery)
  9. Disruption of stratum corneum using ultrasound
  10. Jet injections (squirt the liquid under high pressure directly into the tissue without the needles)
  11. Through the nose or mouth by breathing the vaccine in
  12. Through the eyes (used in poultry )
But why we don't just drink water with the vaccine?!

I am joking, but seriously, why do we still use needles?
What could be the next standard in vaccination, now when mass vaccinations are increasingly likely?


[1]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310953/

[2]https://www.researchgate.net/publication/233536605_Intraocular_vaccination_with_an_inactivated_highly_pathogenic_avian_influenza_virus_induces_protective_antibody_responses_in_chickens

immunologybiotechvaccination
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Creative contributions

The problem with oral vaccines

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Subash Chapagain
Subash Chapagain Nov 30, 2020
Despite being the easiest and patient-approved route of administration, oral vaccines are still not the most widely used in terms of safety and efficacy because of some of the inherent limitations owing to the barriers posed by the gastrointestinal system. Mainly three things are crucial for the success of a vaccine when delivered orally:
  • delivery of intact and active antigen to the intestine
  • transport across the mucosal barrier
  • and the eventual activation of APC (antigen presenting cells) that activate CD4 T-cells .
The GI tract poses hindrances to each of these above steps, as it has a very hostile environment mainly developed for breaking down and digesting whatever finds a place within it. Firstly, the physical-biological barrier of the intestinal epithelium and mucus-secreting layers works as a shield. These layers work to digest consumed substances for nutrient absorption, by the virtue of the highly acidic environment as well as the presence of a number of proteolytic enzymes that degrade proteins and peptides. These features of the GI tract can greatly interfere with the delivery of the antigens/proteins/peptides that we want to administer as the vaccine . Moreover, the time period available for oral formulations presents another limitation to their success. The residence time for such orally given vaccines is just around 3-4 hours (the standard time for absorption) which might not always be enough for the vaccine to be accumulated to APCs in enough amount so that a successful immune response could be triggered .

There are other additional downsides as well. For example, for oral vaccines, we might need to deliver a higher dose than their non-oral counterparts which imminently narrows down the choice of delivery vehicles (vectors) for the antigen . Moreover, larger doses always have the risk of inducing tolerance rather than stimulating a protective response, a number of studies have shown .



[1]Mitragotri S, Burke PA, Langer R, Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies, Nat. Rev. Drug Discov 13 (2014) 655–672.

[2]Renukuntla J, Vadlapudi AD, Patel A, Boddu SHS, Mitra AK, Approaches for enhancing oral bioavailability of peptides and proteins, Int. J. Pharm. 447 (2013) 75–93

[3]Mudie DM, Amidon GL, Amidon GE, Physiological parameters for oral delivery and in vitro testing, Mol. Pharm 7 (2010) 1388–1405.

[4]Pavot V, Rochereau N, Genin C, Verrier B, Paul S, New insights in mucosal vaccine development, Vaccine 30 (2012) 142–154.

[5]Davitt CJH, Lavelle EC, Delivery strategies to enhance oral vaccination against enteric infections, Adv. Drug Deliv. Rev 91 (2015) 52–69.

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jnikola
jnikola3 years ago
I agree with all the mentioned problems of oral vaccines, but the reason why I think the efforts must be made in terms of upgrading the oral vaccines and their administration is the fact that the efficacy and general performance of the vaccine depend on the solutions in three areas:
- production ("formula", packaging, distribution, ...)
- mode of action (efficiency)
- waste management

Although the "needle" vaccines present the best solution in terms of the "mode of action" part, their production and waste management costs are enormous. They require high purity, a sterile environment, trained personnel, and generate a lot of biohazardous material, which is not easily manageable, especially in third-world countries.
On the other hand, oral vaccines show incredible potential in production (distribution, self-administration, lower purity = lower costs of production) and waste management, thus offering a giant reduction of costs, which can be then repurposed for the R&D (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132247/).

To conclude, the biggest problem of oral vaccines is, as you mentioned, the GI tract. I think the development of novel delivery systems based on adenoviruses or liposomes could be the key to increase the absorption and efficacy of oral vaccines.
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General comments

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Povilas S
Povilas S3 years ago
This article explains it pretty well: https://www.forbes.com/sites/quora/2017/11/07/why-arent-vaccines-given-intravenously/?sh=2e1bb8a4798c
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