Immunology - Vaccines

How did Pasteur created his attenuated cholera?

He grew a version of cholera that grew in warmer temperatures (who found the chicken's internal body temperature too cold)

Define: Passive Immunity

Passive immunity is achieved by preformed immunoglobulins from previously infected or immunized individuals.
It provides immediate immunity, but dissipates after a few weeks or months because the antibodies do not regenerate.

Does passive immunity generate memory?

No

Give examples of natural vs induced passive immunity.

Natural passive immunity is acquired by the transfer of maternal antibodies to a fetus. Induced passive immunity comes from the transfer of antibody from one individual to another.

What is Intravenous Immunoglobulin?

Plasma from healthy folk are given to sick people to help them fight an infection. The non-specific antibody contains a mixture of antibodies that reflects the prior exposures of the donor to various antigens.

Define Immunization

*Gaining* protective immunity through exposure to a pathogen

Define Vaccination

Intentionally exposing an individual to a pathogen (or part of a pathogen), with the *intention of generating* protective immunity

What are (4) reasons why vaccination may not lead to protective immunity?

Administration Errors, pathogen changes, genetics, batch quality

How are genetics a factor in whether vaccination leads to immunity?

MHC is the most diverse aspect of humans. Some MHC molecules work better or worse than others for some vaccines. Not all MHC recognize all vaccines.

Why is induced active immunity better than natural active immunity?

Vaccines, compared to the pathogen, are non-communicable, more controlled, better tested, and just generally safer

List (6) types of potential antigens for a vaccine

Live-attenuated, killed, subunit, toxoid, genetically engineered, DNA/RNA

Vaccination against ____ common childhood illnesses has saved _____ million lives

9, 6

How many diseases have ever been eradicated?

1

What are the three components of a vaccine?

Antigen, adjuvant, route&dose

Discuss Live-attenuated Vaccines

They use a weakened or less virulent version of a pathogen that will actually infect and replicate within the host.
They induce a strong cellular and humoral response.
They have the potential to revert to active pathogen.
They cannot be given to health professionals or the immunocompromised.
They must be refrigerated to stay potent.
It is difficult to create LAVs against bacteria because bacteria have much more genes and are much harder to control.

Discuss Killed vaccines

They contain the inactivated organism.
They are unable to infect the host.
They provide no risk of vaccine associated infection, while still providing many antigens.
Components often consist of surface molecules that mediate host cell invasion
Produce weaker, shorter-lived immunity
Often requires multiple boosters
Stable, don't need to be stored at cold temperatures

Discuss Subunit Vaccines

These vaccines use antigens (targets) that best stimulate the immune system.
They elicit antibody but not cytotoxic T-cell response
They struggle to work against pathogens that are antigenically diverse and variable

Discuss Toxoid Vaccines

These vaccines target a toxin, rather than the bacteria that's secreting the toxin.
They are used when the toxin is the main source of illness and the bacteria isn't that bad on its own.
Chemically altered toxins or bacteria that produce harmless variants of the toxin are injected into the body, and antibodies are produced against the toxin

Engineered Vaccines (AKA recombinant factor)

Genes that encode microbial antigens are introduced into the genome of a non-cytotoxic or attenuated virus/bacteria.
It generates a true infection and results in robust, long-lasting immunity.
It elicits the full complement of immune responses, including strong Cytotoxic T-cell responses
No exposure to the virulent pathogen

DNA/RNA vaccines

These vaccines contain no pathogen.
They contain a gene encoding a pathogen target.
The gene of the antigen of interest is cloned into a bacterial plasmid that is engineered to increase expression of the inserted gene in mammalian cells.
After being injected, the plasmid enters a host cell where it uses host cell protein synthesis machinery to carry out synthesis of the protein it encodes
- The microbial protein may be presented in the context of MHC molecules to elicit T-cell response
Engages innate cell receptors
Can be engineered to target non-immunodominant epitopes
Easy to produce and purify
Low Cost

What are immunodominant epitopes?

These are the epitopes that are most easily recognized by the immune system, and thus, most influence the specificity of the induced antibody

Theoretical concerns of DNA/RNA vaccines

- Potential for host chromosome integration and induction of mutagenesis and insertional carcogenesis
- Potential for induction of anti-ds-DNA antibodies--- leading to autoimmune disease

List (7) problems with relying on natural immunity

can't control dose, low risk group may infect high risk individuals, higher virus levels makes it more difficult to protect high risk groups, who is high risk, unclear protection duration, emergence of new viral variants, people still get sick

What are three mechanisms of adjuvants and explain them.

- Stimulate Immune Response: by stimulating macrophage activity, which can help activate TH1 cells. Adjuvants can also stimulate lymphocyte proliferation. But can also cause local chronic inflammation and granuloma formation.

- Prolong Exposure : an antigen can bind to and precipitate an antigen to keep it in the system longer, allowing for slow release of the antigen. This increases the time of exposure and can drive an immune response for weeks.

- Co-stimulatory Signal : TH cells, when stimulated by antigens, require a second signal to tell the TH cells to respond. Without presentation of this cosignal, the T-cell will ignore the antigen. Adjuvants can up-regulate co-stimulatory signal systems.

What are adjuvants?

Substances that, when injected with an antigen, serve to enhance the immunogenicity of the antigen - leading to a higher antibody titre and a longer lasting immune response.

What is herd immunity?

When the percentage of population immunized is high enough that there is limited and non-sustained spread of an infection

Why have vaccination rates been decreasing?

- Misinformation
- Fear mongering
- Naturopathy
- Apathy/Naivety

_____% of Canadians are vaccine hesitant. _____% of Canadians are vaccine refusers.

20, 5

Vaccine hesitancy is due to factors such as...

- the anti-vaccine movement
- misinformation and social media
- lack of disease
- laziness
- politics