Week 4 (Part 3): Vaccines in Canada

Question 1

Define immunization vs. immunoprophylaxis.:

Answer 1

Immunization refers to the process by which a person becomes protected against a disease through exposure to immunizing agents.

Prevention of disease through the use of immunizing agents is called immunoprophylaxis.

Question 2

What types of immunization agents are there?

Answer 2

Active and passive

Question 3

Describe active immunization:

Answer 3

Active immunization is the inherent production of antibodies against a specific agent after exposure to the antigen through vaccination.

• Stimulation of the immune system
• Unlike passive, it lasts many years or lifetime

Acquire – survive infection of the disease-causing organism (immunologic memory)
- Memory B and T Cells – upon re-exposure, develop to provide protection

Active immunizing agents are typically referred to as vaccines.

Influenced by:

• Maternal antibodies
• Route of administration
• Host factors
• Nutritional factors
• Co-existing diseases

Question 4

Describe passive immunity:

Answer 4

Passive immunization involves the transfer of pre-formed antibodies, from one person to another or from an animal product, to provide immediate, temporary protection from infection or to reduce the severity of illness caused by the infectious agent.

• Protection provided by passive immunization is temporary because the transferred antibodies degrade over time.
• Passive immunization can occur by transplacental transfer of maternal antibodies to the developing fetus, or it can be provided by systemic administration of a passive immunizing agent.
• Passive immunization with immune globulins provides protection when vaccines for active immunization are unavailable or contraindicated, or in certain instances when unimmunized individuals have been exposed to the infectious agent and rapid protection is required (post-exposure immunoprophylaxis)

Question 5

What might immunizations include in addition to the active component?

Answer 5

In addition to the active component (antigen in case of vaccines or antibody in case of immunoglobulins), immunizing agents may contain additional ingredients such as preservatives, additives, adjuvants and traces of other substances.

Question 6

What are vaccines designed to do?

Answer 6

Vaccines are complex biologic products designed to induce a protective immune response effectively and safely.

Question 7

The ideal vaccine?

Answer 7

An ideal vaccine is: safe with minimal adverse effects; effective in providing lifelong protection against disease after a single dose that can be administered at birth; inexpensive; stable during shipment and storage; and easy to administer.
- Some vaccines come closer to fulfilling these criteria than others.

Question 8

How long does a vaccine take to market?

Answer 8

10-15 years

Question 9

How do Vaccines work to produce individual immunity?

Answer 9

Administration of a vaccine antigen triggers an inflammatory reaction that is initially mediated by the innate immune system and subsequently expands to involve the adaptive immune system through the activation of T and B cells.

• While the majority of vaccines provide protection through the induction of humoral immunity (primarily through B cells); some vaccines, such as BCG and live herpes zoster vaccines, act principally by inducing cell-mediated immunity (primarily though T cells).
• Many vaccines probably work through both, although humoral immunity is the basis most often used as a marker of how well a vaccine works.

Question 10

What does long-term immunity require?

Answer 10

Long-term immunity requires the persistence of antibodies, or the creation and maintenance of antigen-specific memory cells (priming) that can rapidly reactivate to produce an effective immune response upon subsequent exposure to the same or similar antigen.

Question 11

What do live attenuated vaccines contain?

Answer 11

Live attenuated vaccines contain whole, weakened bacteria or viruses.

Question 12

Since the agent replicates within the vaccine recipient, the stimulus to the immune system more closely resembles that associated with …

Answer 12

… natural infection, resulting in longer lasting and broader immunity than can be achieved with other vaccine types

Question 13

How do live vaccines achieve immunity in one dose?

Answer 13

Because of the strong immunogenic response, live attenuated vaccines, except those administered orally, typically produce immunity in most recipients with one dose…
- However, a second dose helps to make sure that almost all vaccine recipients are protected, because some individuals may not respond to the first dose.

Question 14

Why must one be careful when handling live vaccines?

Answer 14

Live vaccines require careful storage and handling to avoid inadvertent inactivation.

Question 15

What do non-live vaccines contain?

Answer 15

Non-live vaccines contain whole inactivated (killed) bacteria or viruses, their parts, or products secreted by bacteria that are modified to remove their pathogenic effects (toxoids).

Question 16

Can non-live vaccines cause the disease?

Answer 16

No

Question 17

Why do non-live vaccines require multiple doses and adjuvants?

Answer 17

Because the immune response to non-live vaccines may be less than that induced by live organisms, they often require adjuvants and multiple doses

• The initial doses prime the immune system and are called primary vaccination or the primary series.
• As protection following primary vaccination diminishes over time, periodic supplemental doses (booster doses) may be required to increase or boost antibody levels.

Question 18

What enhances the immune response of non-live diseases?

Answer 18

The addition of adjuvants to non-live vaccines enhances the immune response and extends the duration of B and T cell activation.

Question 19

The type of vaccine antigen and its immunogenicity directly influence the nature of the immune response that is induced to provide protection:
- Live vs. non-live vs. pure polysaccharide?

Answer 19

1) Live attenuated vaccines generally induce a significantly stronger and more sustained antibody response.
2) Non-live vaccines often require adjuvants to enhance antibody responses, usually require multiple doses to generate high and sustained antibody responses, and induce vaccine antibodies that decline over time below protective thresholds unless repeat exposure to the antigen reactivates immune memory.
3) Pure polysaccharide vaccines induce limited immune response and do not induce immunologic memory.

Question 20

What is the third type of vaccine?

Answer 20

third type of vaccines are subunit vaccines and include toxoid, recombinant, polysaccharide, and conjugate vaccines use specific pieces of the germ — like its protein, sugar, or capsid (a casing around the germ).

• It is a much more sophisticated product, a purified bacterial component
• In both these cases, it is a protein toxin previously demonstrated to be an essential cause of the disease. - For the vaccine, the toxin is chemically modified to yield the non-toxic toxoid.
• Conjugating (linking) a polysaccharide with a carrier protein (protein that is easily recognized by the immune system such as diphtheria or tetanus) leads to a significantly higher immune response.

Question 21

What is a live attenuated vaccine?

• What does it express?
• How does it replicate?
• What is it identical to?
• One dose?
• Reactions possible?
• Fragile?
• Viral vs. Bacterial?

Answer 21

Microorganism is attenuated (weakened)

• Still expresses its surface antigens
• It replicates in a vaccinated individual, but slower - must replicate to produce an immune response
• Immune response virtually identical to natural infection
• Usually produce immunity with one dose except those administered orally
• Severe reactions possible
• Fragile – must be stored carefully
• Viral: Measles, mumps, rubella, vaccinia, varicella, zoster, yellow fever, rotavirus, intranasal influenza, oral polio
• Bacterial: BCG, oral typhoid, rotavirus

Question 22

Live attenuated vaccines:

• Advantages
• Disadvantages
• Unlikely?

Answer 22

Advantages: Mimics natural infection
- Develop T cell & B cell long-term protective immunity
- Long-term immunity usually achieved with one low dose
raise immune responses to all antigens/multiple epitopes

Disadvantages
- Usually requires refrigeration → storage issue in developing countries

UNLIKELY but:

• could spread to susceptible persons
• cannot be used in immunodeficient or pregnant people
• may revert back to a virulent form

Question 23

Live vaccines are technically unachievable for most vaccines under development:

Answer 23

• Under-attenuated = cause disease

- Over-attenuated= does not provoke an immune response

Question 24

Inactivated vaccines are used with microbes that:

Answer 24

1) cannot be attenuated

2) have oncogenic potential

Question 25

What are inactivated vaccines composed of?

• How are they grown and activated?
• Advantages?

Answer 25

Virus or bacteria or fractions of both

They are not alive and cannot replicate

• Grown in culture media and activated with heat
• Organism purified to be contained in vaccine

Advantage

• Microbe cannot revert to a virulent form, so it cannot cause disease
• safer than live attenuated vaccines
• can be used with immunodeficient patients

Question 26

What do inactivated vaccines require?

Answer 26

Always require multiple doses

• First dose primes
• Second dose creates immune response

Question 27

What type of immune response do inactive vaccines produced?

Answer 27

Immune response to inactive vaccine is mostly humoral

Question 28

What is the cause of disease?

- What is the case for the polysaccharide vaccine, what is yielded?

Answer 28

In both these cases, it is a protein toxin previously demonstrated to be an essential cause of the disease
- For the vaccine, the toxin is chemically modified to yield the non-toxic toxoid.

Question 29

What is the response of polysaccharide vaccines?

Answer 29

T-cell independent response, vaccine an stimulate B-cells without help of T-helpers cells; young children to not respond consistently due to immaturity of their immune system; repeat doses do not cause a booster response because antibody in response to polyssach vaccines is IgM and little IgG is produced – can be over come by conjugation (changes immune response to T-dependent, increased immunity in infants and booster response to multiple doses of the vaccine)

Question 30

Conjugate Vaccines:

Answer 30

A conjugate vaccine is a type of vaccine which combines a weak antigen with a strong antigen as a carrier so that the immune system has a stronger response to the weak antigen

• Conjugate Vaccines are against polysaccharides
• Inactivated vaccines
• Zero risk of disease: have highest safety record safe for immunocompromised persons
• polysaccharide antigen is conjugated to a protein to “make” B cell bind to a T cell.

Question 31

Conjugate Vaccines: Disadvantages

Answer 31

• Stimulates a weaker immune response than live vaccines
• Requires a larger dose and multiple boosters to generate long-term immunity
• vaccine requires an adjuvant: - An adjuvant is a substance that is added to a vaccine to enhance the resulting immune response and to extend the duration of B and T cell activation.
• An adjuvant allows a reduction in the amount of antigen per dose or the total number of doses needed to achieve immunity, and helps to improve the immune response in individuals with some degree of immune suppression (for example, the elderly). (ie aluminum salts)

Question 32

What do toxoid vaccines do?

Answer 32

They are against bacterial toxins
- Use a toxin made by a germ that causes the disease to create immunity to parts of that germ that cause the disease rather than the germ itself

• Immune response targeted to toxin
• Rendered harmless to elicit immunity
• TO increase immune response (Ca or Al salts)
• Safe – does not cause the disease, or reversion to virulence - Does not spread to unimmunized individuals; stable, less susceptible to environmental factors
• Requires several doses
• Ajuviment required as they are not highly immunogenic on their own

Question 33

What are next generation vaccines?

- Example

Answer 33

Nucleic acid-based vaccines

• Introduce microbial DNA that encodes for one or more microbial antigens into host cells
• host cell will then generate the microbial antigen(s), which will then be displayed on its surface.
• Generate both B and T cell immunity

COVID-19

• mRNA is used and contains material from the virus and gives cells instruction to make harmless protein unique to the virus and the genetic material is then destroyed from the vaccine
• Body recognizes this protein should not be there and our body develops B and T lymphocytes that will remember how to fight the virus that causes COVID-19 if we were ever to be infected in the future

Question 34

What prevents vaccination?

Answer 34

availability to underdeveloped countries

vaccine safety fears/public trust

vaccine development

Question 35

Challenges with vaccines in the future:

Answer 35

Many vaccines are not effective in immunocompromised people.
Approach: adjuvants or new vaccine delivery systems

Antigenic variation due to mutations requires constant updating of vaccine formulations.
Approach: seek conserved antigens; monitor genetic variation

High costs of vaccine development result in premature abandonment of potentially useful ones
Approach: investment in vaccine research

Inadequate access to and availability of vaccines in poor countries.
Approach: Tiered pricing strategies; facilitate vaccine development