Viral Vaccine Development Flashcards
Importance of Viral vaccines
- Protection of population groups from the symptoms
- Control of the spread of diseases
- Elimination and eradication of a disease
What makes a vaccine an important and feasible target for vaccine development?
- Infection is serious enough to warrant vaccine development
- Limited number of serotypes
- Virus does not mutate rapidly
- The natural infection is acute and self-limiting, and the immunity that follows is long lasting
Prophylactic or Therapeutic Vaccines
Vaccine Safety:
Vaccine Efficacy:
Practical Considerations:
Vaccine Safety: Should not cause illness/post a threat
Vaccine Efficacy: Long-lived immunity; elicit humoral immunity; elicit cell-mediated immunity
Practical Considerations: Cost; shelf-life; ease of distribution; few side effects
Immunological Principles (How adaptive immune response works)
- Presentation of immunogens by proffesional APCs drives an efficient immune response
- As the dose of antigen increases, the number of naive lymphocytes that respond increases
- Once naive lymphocytes have responded with 10-15 cell divisions, they must “rest” - can be re-stimulated to proliferate again
Immunological Principles (Different types of immune responses and induction of response)
Cellular and humoral immunity - relative importance differs for different viruses
The formulation o antigen, the route of immunization, and the adjuvant used affect the balance of cellular vs. humoral response (TH1 vs. TH2)
Presentation of antigen to MALT system is important for the induction of mucosal immunity
First Goal of vaccination:
To generate “neutralizing antibodies” which can lead to
- Direct neutralization
- Complement-mediated virolysis
- Complement-mediated phagocytosis and inactivation
Antibodies can bind to viral antigens on the surface of infected cells leading to:
- Cell lysis
- Inhibition of viral replication, release or spread
Protection afforded by passive transfer of antibodies can:
Rarely:
More Often:
Rarely: Generate sterile protection – lead to an absence of viral replication
More Often: Blunt infection sufficiently to allow other facets of immune response to take over
Why don’t viruses evolve surface structures that fial to elicit neutralizing antibodies?
- Repetitive viral surface antigens often elicit the best neutralizing Abs - highly organized virion surfaces
- Viruses that elicit strong neutralizing Ab responses must NOT have been subjected to contrary evolutionary pressure
- They must be transmitted quickly from host to host before antibodies can coat progeny virus
- They must not “rely” on re-infection of same individuals
What is the importance of mucosal immunity?
- Recognize and combat infection at portal of entry
- Affected by type of vaccine
- Affected by route of administration
- Target antigen delivery to mucosal cells
- Target antigen uptake by APC and trafficking to correct lymphoid compartments
POLIO - prevention and control - inactivated virus vaccine
Advantages:
Disadvantages:
Advantages:
- Cannot undergo genetic mutation to increase virulence
- Safe for immunocompromised people
Disadvantages:
- Fails to elicit gut immunity
- Requires parental administration
- Expensive
- Requires boosters
- Must ensure potency and inactivation
Inactivated Vaccines
Virus preparations that are chemically/physically inactivated
- Elicit circulating antibodies, but no mucosal immunity
- Longevity of immune response is still controversial
POLIO - Prevention and Control - Live attenuated Vaccine
Advantages:
Disadvantages:
Advantages:
- Inexpensive and easy to administer
- Induces both systemic and secretory immunity
- Induces herd immunity
Disadvantages:
- Can mutate to more virulent strain
- Less reliable in tropical climates (needs to be kept cold)
Goal of Live, attenuated vaccines
To mimic natural infection without causing disease
Creation of an “attenuated strain”
- Pathogenic virus is isolated from a patient and grown in culture human cells
- Cultured virus is used to infect monkey cells
- The virus acquires many mutations that allow it to grow well in monkey cells
- The attenuated virus no longer grows well in human cells - vaccine
