11. Vaccine Design Flashcards
Structure of the lecture
- Components of vaccine design
- Major vaccine successes and their factors
- Major limitations in vaccine sucess
- Future of vaccines
What are the aims of vaccination?
1.1
Classical vaccine immunology aims to prime the immune system via generating long-lasting protective immune memory. This is so that subsequent, natural infection is less damaging
What are the 5 major stages to release of a vaccine?
1.2
- Preclinical studies
- Clinical studies (Phase I to test immunogenicity, Phase II to test safety, Phase III is double-blind, placebo-controlled)
- Licensing and regulatory approval
- Approval for use
- Implementation, distribution, monitoring etc.,
What are the 6 different types of virus?
1.3
- Inactivated pathogen
- Live attenuated
- Purified component
- Modified components
- Viral-vectored
- mRNA
What are the components of a vaccine (like what’s in the actual vial)?
1.4
Antigen(s)
Stabilisers
Adjuvants
Preservatives
Residual chemicals from production
What is the function of vaccine adjuvants?
1.5
Have either a carrier or depositor y effect, and can be biological or chemical in nature. Only 6 are approved for human use.
What are the 3 major successes of global vaccination?
2
- Herd immunity
- Childhood vaccination programmes
- Global eradication programmes
List some success herd immunity programmes
2.1
Herd immunity aims to priortise the health of the population to provide health to the individual
- Acellular Diptheria vaccine provided accidental herd immunity in the 1950s
- H. influenzae is an example of waning herd immunity
- B. pertussis vaccine shows how misinformation can limit herd immunity
- MMR vaccine shows the importance of inducing herd immunity in young children
- Mumps shows the importance of catch-up campaigns, since many individuals in their 20s become susceptible after no effect follow up and waning herd immunity
List some examples of successful childhood immunity projects?
2.2
- DPT, which afford protection against Diptheria, B. pertussis and tetanus, and relies on building antivodies very young
- MMR, which is a very common/successful vaccine
List two examples of eradication programmes
2.3
- Smallpox - the only human disease to have been successfully eradicated. Can be attributed to the fact it only has a single antigenic type, and there is easy access to a successful weakened version (cowpox)
- Polio - getting there!
What are the 6 major limitations to vaccine success?
3.1
- Pathogen variability
- Vaccine safety
- Environmental and geographical factors
- Host variability
- Lack of understanding of the human immune system
- Misinformation
What can lead to pathogen variability?
3.1
Driven by pathogen diversity, antigenic shift/drift, hypervariability, active/latent infection, immune evasion
What is limiting vaccine safety?
3.2
Adverse events, autoimmunity, contamination of vaccines, advers-onomics.
Can lead to vaccine hesitancy
How are environmental/geographical effects limiting vaccine success?
3.3
Poor nutrition
Co-infection
Prior infection (Original antigenic sin/immune imprinting)
Access to healthcare
How is host variability limiting vaccine success?
2.4
Inter-individual variability
Non-responder populations
Age/sex ethnicity etc.,
How is a lack of understanding of the immune system limiting vaccine success?
3.5
Unable to generate effective and adequate immune responses
How is misinformation limiting vaccine success?
3.6
Dominated by media mis-representation, individuals like RFK Jr, and can lead to vaccine hesitancy
What are the 3 major limitations to mRNA vaccine success?
3.7
- Inefficiency of the 5’ Cap, which limits innate sensing and protein production of the vaccine
- CDS sequences often need modification
- 3’ PolyA tail is impacted by properties like length, which can limit protection
How is the success of vaccine programmes for ‘The Big Three’ being limited?
3.8
Malaria: Hard to choose the correct antigen, and generate a strong enough immune response, and avoid immune escape
HIV-TB Co-pandemic: MVA85A vaccine for TB got all the way to Phase III, but was then shown not to be better than the placebo
What are the main ways that we can improve vaccine success?
4
- Reverse vaccinology (use of genomics to work backwards)
- Improving speed (seen in COVID-19. Improving with rapid-sequencing)
- Improvement of existing vaccines (BCG vaccine for TB is ineffective in adult pulmonary vaccines, so needs updating)
- **Development of new platforms **(e.g., mRNA)
