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Flashcards in Viral Vaccine Development Deck (22):
1

Importance of Viral vaccines

  • Protection of population groups from the symptoms
  • Control of the spread of diseases
  • Elimination and eradication of a disease

2

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

3

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

4

Immunological Principles (How adaptive immune response works)

  1. Presentation of immunogens by proffesional APCs drives an efficient immune response
  2. As the dose of antigen increases, the number of naive lymphocytes that respond increases
  3. Once naive lymphocytes have responded with 10-15 cell divisions, they must "rest" - can be re-stimulated to proliferate again

5

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

6

First Goal of vaccination:

To generate "neutralizing antibodies" which can lead to

  • Direct neutralization
  • Complement-mediated virolysis
  • Complement-mediated phagocytosis and inactivation

7

Antibodies can bind to viral antigens on the surface of infected cells leading to:

  • Cell lysis
  • Inhibition of viral replication, release or spread

8

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

9

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

10

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

11

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

12

Inactivated Vaccines

Virus preparations that are chemically/physically inactivated

  • Elicit circulating antibodies, but no mucosal immunity
  • Longevity of immune response is still controversial

13

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)

14

Goal of Live, attenuated vaccines

To mimic natural infection without causing disease

15

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

16

Alternative approach: Recombinant Viruses (Goal)

Goal: to generate viral vector that carries genes from one or more additional viruses

  • Establish immunity to multiple infectious agents at once
  • Take advantage of features of a virus that make it a "good" vaccine
  • Example: Influenza Vaccine (generate and transfect desired RNAs into cells)

17

Subunit or recombinant vaccines (the 2nd genearation)

  • Avoid the requirement for total inactivation of live virus in preparation
  • Cost/difficulty in production may be a drawback
  • Ex: HBsAG - subunit vaccine

18

Human Papillovirus (HPV) vaccine:

  • HPV types 16 and 18 cause 70% of cervical cancer cases
  • Quadrivalent HPV L1 VLP vaccine (Types 6, 11, 16, 18)
  • Yeast - or - cell-derived L1 protein of the viral capsid

19

Alternative Approaches (Peptide-based)

  • Identify immunodominant epitopes - for neutralizing antibodies/presentation on MHC I and II
  • Generate peptide-based vaccines
    • Can be indtroduced in a formulation that stimulate cellular uptake, or with adjuvants that stimulate immune responses

20

Antigens can be enigineered to have altered ______ for MHC or TCR

affinity

21

DNA inoculation (Goal)

Goal: introduce DNA encoding antigens into appropriate tissues

  • DNA taken up into cells; proteins expressed
  • Genes "customized" to provide secreted antigens

22

____ sequences within plasmids act as immunological adjuvants for DNA innoculation

CpG