Unit 15: Vaccines

define vaccines

biologically derived agents designed to stimulate an immune response preventing or reducing the severity of disease upon further infection

define vaccination

the act of administering a vaccine

define immunization

the process by which an individual becomes immune to a disease (often through vaccinations)

what is the importance of vaccines

• protect individuals from preventable diseases to reduce morbidity / mortality rates

• protect the community / herd immunity

• eradicating & controlling diseases

• reduce healthcare cost

define eradication in reference to the importance of vaccines

permeant to zero of the incidence of infection (smallpox)

how does herd immunity work

• breaks the chain of transmissions

• protecting the vulnerable

• reducing outbreaks

• disease elimination & eradication

what is R0

a metric that describes the average number of secondary infecctions that a single infected individual would generate

detail R0>1

• one person will infect more than 1 individual

• indicates that the disease has the potential to spread quickly

  • Ex. Measles (R0 12-18); Mumps (R0 10-12); COVID 19 (R0 2-3); Omicron Variant (R0 8.2)

how do vaccines influence the R0 of an infectious disease

• reduce the susceptible population

• lowering the R0 to < 1

• achieving herd immunity

define Herd Immunity Threshold (HIT)

proportion of the population that needs to be immune to prevent sustained spread

detail live attenuated vaccines

• contain live but weakened (attenuated) forms of pathogens

• attenuated pathogen can still replicate within the host (slower and less replication)

• replication triggers a robust and long lasting immune response

  • Ex. MMR

detail the advantages of live attenuated vaccines

• often provide lifelong immunity with one or two doses

• elicit a broad immune response (humoral and cell-mediated)

detail the disadvantages of live attenuated vaccines

• Potential for reversion to virulence (extremely rare)

• Not suitable for immunocompromised individuals due to the risk of uncontrolled replication 

• May require refrigeration (cold chain), posing logistical challenges 

• Possible mild symptoms resembling the disease 

detail inactivated vaccines

• Contains killed (inactive) pathogens 

• Inactivation destroys the pathogen’s ability to replicate but preserves its antigens (stimulating an immune response)

  • Ex. Polio Vaccine

detail the advantages of inactivated vaccines

• Generally safer than live vaccines

• More stable and easier to store

• Can be used in immunocompromised individuals

detail the disadvantages of inactivated vaccines

• Stimulate a weaker immune response compared to live vaccines.

• Often require multiple doses (booster shots)

• Immune response is primarily humoral (antibody-mediated).

detail subunit vaccines

• Contains specific antigen components of pathogens to prompt targeted immune responses

• Antigens are carefully selected to elicit a protective immune response

  • Ex. Hepatitis B vaccine

detail the advantages of subunit vaccines

• High safety profile

• Targeted immune response

detail the disadvantages of subunit vaccines

• May require adjuvants to enhance immunogenicity

• Can be more complex and expensive to produce

• May not elicit as broad an immune response as live vaccines

detail recombinant vaccines

• Produced using genetic engineering techniques

  • Antigen genes are inserted into the genome of another organism (yeast, bacteria)

  • Host organisms then produces the antigen in large quantities

    • Ex. Human papillomavirus (HPV) vaccine

detail the advantages of recombinant vaccines

• High purity and safety

• Can be used to produce vaccines against pathogens that are difficult to culture

detail the disadvantages of recombinant vaccines

• May require adjuvants

• Complex production process

detail conjugate vaccines

• Designed to improve the immunogenicity of polysaccharide antigens

  • Polysaccharides often elicit a weak immune response

    • Polysaccharide antigens are chemically linked to a protein carrier

    • Converts the polysaccharide into a T-dependent antigen

      • Make immune response stronger and longer lasting

  • Ex. Haemophilus influenzae type b (Hib) conjugate vaccine.

detail the advantages of conjugate vaccines

• Significantly enhance the immune response to polysaccharide antigens

• Provide long-lasting protection

detail the disadvantages of conjugate vaccines

• More complex to produce than some other vaccine types

detail toxoid vaccines

• Used to protect against diseases caused by bacterial toxins

  • Bacterial toxins are purified and then detoxified (inactivated) to create toxoids.

    • Toxoids still retain their antigenic properties, stimulating the immune system to produce antibodies that neutralize the toxin.

    • Ex. Tetanus toxoid vaccine

detail the advantages of toxoid vaccines

• Highly effective at preventing diseases caused by bacterial toxins

• Very safe

detail the disadvantages of toxoid vaccines

• Protection is specific to the toxin, not the bacteria.

• May require booster doses to maintain immunity.

detail mRNA vaccines

• mRNA molecules encoding the antigen are encapsulated in lipid nanoparticles and delivered to cells

  • Host cells translate the mRNA into the antigen.

  • Ex: COVID-19 vaccines (Pfizer-BioNTech, Moderna).

detail the advantages of mRNA vaccines

• Rapid and inexpensive to design and produce

• Can elicit both humoral and cell-mediated immunity

• Can be modified quickly (if the pathogen mutates)

detail the disadvantages of mRNA vaccines

• mRNA vaccines may require cold or ultra-cold storage

• Long-term effects are still being studied

detail viral vector vaccines

• Use a harmless virus (the vector) to deliver genetic material encoding the antigen from another pathogen

  • Vector virus is modified so that it cannot cause disease

    • Once inside the host cells, the gene is expressed, and the antigen is produced, triggering an immune response

  • Ex. COVID-19 vaccines (AstraZeneca, Johnson & Johnson)

detail the advantages of viral vector vaccines

• Can elicit strong humoral and cell-mediated immunity.

• Can be used to deliver large or complex antigens.

detail the disadvantages of viral vector vaccines

• Pre-existing immunity to the vector can reduce vaccine effectiveness.

• Potential for rare adverse events (e.g., blood clotting with some adenovirus vectors)

who was the person to develop the first true vaccine and what was it for

Edward Jenner - smallpox

detail the Exploratory Stage of the pre-clinical phases of vaccine development

• 2-5 years

• Focus: identify potential antigens that could be used in a  vaccine 

• Involves the understanding the disease, the pathogen causing it, and how much the immune system responds 

detail the Pre-clinical Stage of the pre-clinical phases of vaccine development

• 1-2 years

• Focus: testing the vaccine candidate in the lab and on animals to assess its safety and immunologicity 

  • In vivo and in vitro testing (human cells and animal models)

  • Evaluating safety and immunogenicity (short term)

  • Develop formulation and manufacturing 

detail Phase 1 of the clinical phases of vaccine development

• approx 2 years

• 20-100 healthy volunteers

• focus on safety and dosage

detail Phase 2 of the clinical phases of vaccine development

• 2-3 years

• 100-300 diverse volunteers (randomized and controlled)

• Includes individuals that are similar to the intended recipient of the vaccine 

• Evaluation of safety and immunogenicity; dosage refinement

detail Phase 3 of the clinical phases of vaccine development

• 5-10 years

  • can be shorter, especially in urgent situations

• 1000s of volunteers (different geographic locations and diverse)

  • Randomized, placebo-controlled, and often double-blinded to minimize bias 

  • Evaluating efficacy and long-term safety 

detail the Regulatory Review and Approval post-clinical phase of vaccine development

• up to 2 years

• Submit a Biologics License Application to the regulatory authority 

• Data is reviewed from pre-clinical and clinical 

• Regulatory authority conduct their own tests and inspect manufacturing facilities 

detail the Manufacturing and Scaling Up post-clinical phase of vaccine development

• Manufacturing process is scaled up to produce large quantities of the vaccine

• Must adhere to strict regulatory requirements and Good Manufacturing Practices (cGMP)

detail the Quality Control and Post-Market Surveillance post-clinical phase of vaccine development

• Monitor vaccine safety and effectiveness after it is released to market

how was the COVID-19 vaccine produced so quickly

• prior research and existing technology

  • mRNA vaccines had been studied for decades

• global collaboration and data sharing

• unprecedented funding

• streamlined regulatory process

what are the 3 Cs of vaccine hesitancy

• confidence

• complacency

• convenience

how do we address vaccine hesitancy

• communication is key

• improving vaccine access and convenience

• public education campaigns

• community engagement and outreach

• building trust and transparency

detail the Universal Influenza Vaccine future area of vaccine research

• Vaccines that provide broad protection against multiple strains of influenza

detail the Cancer Vaccine future area of vaccine research

• Exploring both preventative vaccines (e.g., HPV) and therapeutic vaccines designed to stimulate the immune system to target and destroy existing cancer cells.

detail the Newer Vaccine Platforms future area of vaccine research

• DNA Vaccines

• Virus-Like Particle (VLP) Vaccines

• Self-Amplifying RNA Vaccines

• Nanoparticle-Based Vaccines

detail the DNA Vaccines of the Newer Vaccine Platforms

introducing DNA encoding for antigens into cells

detail the Virus-Like Particle (VLP) Vaccines of the Newer Vaccine Platforms

mimicking the structure of viruses but lacking genetic material

detail the Self-Amplifying RNA Vaccines of the Newer Vaccine Platforms

RNA that can replicate within cells, leading to increased antigen production

detail the Nanoparticle-Based Vaccines of the Newer Vaccine Platforms

Encapsulating antigens or genetic material in nanoparticles for enhanced delivery and immunogenicity