vaccine formulation and delivery

what is immunisation

where an individual's immune system becomes strengthened against an agent (known as the immunogen/antigen)

what is vaccination

a method of giving antigen to stimulate the immune response through active immunisation

what is a vaccine

• an immuno-biological substance designed to provide specific protection against a disease. A vaccine is "antigenic" but not "pathogenic".

• ‘Any preparation intended to produce immunity to a disease by stimulating the production of antibodies’ - WHO 

how does a vaccine trigger the immune system 

• vaccine enters the body

• activation of innate immune system 

  • antigen-presenting cells (dendritic cells and macrophages) process the antigen, then migrate to lymph nodes

• activation of adaptive immune system in lymph nodes

  • APCs present antigen to T cells 

  • T cells activated into cytotoxic T lymphocytes

  • B cells activated and turn into plasma cells 

  • fights acute infection

  • memory cells produced for long-term immunity 

what are the properties of an ideal vaccine formulation

• development speed → fast production

• storage temperature → cold-chain independent

• facility of production → LMICs/Transferable technology 

• effectiveness → effective after a single dose 

• administration → needle delivery fit for all age groups 

• scale-up speed → easy to scale-up and affordable 

what is a vaccine delivery system

vaccine formulation + delivery device/route administration = vaccine delivery system 

what are the types of vaccines (antigen type)

• live attenuated vaccine (LAV)

• inactivated vaccine(killed antigen)

• subunit vaccine (purified antigen)

• toxoid vaccine (inactivated toxins) 

• live vector vaccine 

• virus-like particles vaccine

• nucleic acid vaccine

summary of vaccine types and their examples

what are adjuvants and mechanism

activate the innate immunity by acting like pathogen or having similar molecular patterns → can enhance or restore the ability of the immune system to identify a vaccine antigen with subsequent activation of APCs and adaptive immunity

• vaccine without adjuvants → weaker and shorter immune response 

• vaccine with adjuvants → stronger and longer-lasting immune response as it attracts more immune cells to the site

what are the roles of adjuvants

• increase the immunogenicity of weak antigens (to trigger an immune response)

• increase the speed and duration of the immune response 

• strengthens the immune response 

• saves money by reducing the required antigen dose 

• increases mucosal immunity 

• stimulates cellular immunity 

• increases the antigen affinity with the antibody 

• eliminates antigen competition in combination vaccines 

types of excipients in vaccine formulations

what are the different routes for vaccine delivery 

• nasal

• lung

• intramuscular 

• subcutaneous 

• intradermal 

• buccal/sublingual and oral 

advantages and disadvantages of nasal and lung delivery

advantages

• rapid mucosal 'local’ and systemic immune
  response

• increased compliance

• no risk of infection upon injection

• Painless/needleless

• no trained personnel required

disadvantages

• formulation for mucosal barrier 

• low bioavailability 

• fast clearance and degradation

• mucosal irritation 

• spray formulation

advantages and disadvantages of intramuscular delivery 

advantages 

• traditional parenteral route 

• clear guidelines 

• high bioavailability 

• development and manufacture well established 

• acceptable route for adjuvant vaccine formulations

disadvantages

• risk of infection upon needle cross-contamination

• need trained personnel and healthcare infrastructure

advantages and disadvantages of subcutaneous delivery 

advantages 

• high bioavailability 

• development and manufacture well established 

• clear guidelines 

• golden standard for live attenuated vaccines delivery 

disadvantages 

• risk of infection upon needle cross-contamination 

• need trained personnel and healthcare infrastructure 

• high reactogenicity (physical inflammatory response)

advantages and disadvantages of intradermal delivery

advantages

• can vector needleless vaccination 

• high bioavailability and immunogenicity 

disadvantages 

• lack of established guidelines to manufacture and approval 

• need trained personnel and healthcare infrastructure

• necessity of specialised material for delivery 

what are the advantages and disadvantages of buccal/sublingual and oral delivery 

advantages 

• simulation of GIT mucosal immune response 

• increased compliance 

• needleless

• no trained personnel required 

disadvantages 

• formulation for mucosal barrier 

• low bioavailability 

• fast clearance and degradation 

• need high antigen concentration 

why is mucosal vaccination important

most major pathogens enter through mucosal surfaces:

• respiratory 

• enteric → oral-faecal route of infection 

• sexually transmitted 

routes for mucosal immunisation

what is the lipid-based nanoparticle delivery system

a way of packaging and delivering vaccine components (such as antigens, mRNA, or adjuvants) inside tiny particles 

• nanoparticles are small carriers that contain lipids, polymers, virus-like particles (VLPs) etc

• nanoparticles act as vehicles that deliver vaccine components into the body more efficiently than if the antigen were used alone.

how do lipid nanoparticles (LNP) mRNA vaccines work

1. mRNA coding for the desired antigen protein 

2. mRNA released into the cells to produce antigen proteins 

3. activates the immune response against any future attack by the immunogen