24: Vaccines 1

Principle behind a vaccine

Using something less pathogenic to prevent something more pathogenic

What are the two diseases eradicated by vaccination

• Smallpox

• Rinderpest/cattle plague

Why does vaccination produce less diverse and less sufficient protection than a full blown infection

It doesn’t present the whole antigen

What type of immunity do vaccines impart

Active immunity

Types of vaccines

• Heterologous

• Attenuated

• Nucleic acid

What type of attenuated vaccine needs to be conjugated with an adjuvant

Fractionated vaccines with non-protein antigens

How does conjugating a fractionated attenuated vaccine increase adaptive immunity stimulation

Links non-protein antigen targets to proteins that are recognized by the intended host

What part of the adaptive immunity only IDs proteins

T cells and most DCs

What part of the adaptive immunity can ID non-proteins

B cells

Toxoid vaccine

Used a modified toxin with lower bioactivity to activate B and T cells

How does cloning make it faster to produce vaccines

If we can isolate the part of the genome that produces the recognized antigens, we bypass the need to culture the pathogen

Types of clone dependent vaccines

• Fractionated

• DNA vax

• Vector vax

Why do DNA and vector vaccines provide a more reliable response

The DNA is incorporated into host cells, and the Ags are presented as endogenous Ags on MHC I for a complete immune response

Characteristics of a good vaccine

• High antigenicity

• Low side effects

• Strong cellular and humoral stimulation

• Generation of the arm of immune system most effective for the pathogen

• Can tell if vaxxed or infected on diagnostics

• Affordable

• Easy to produce

• Long memory

Relationship between vaccine efficacy and safety

It is a sliding scale, to have more of one you usually have to give up some of the other

Types of vaccines that only produce a humoral response

• Killed/inactivated

• Toxoid

• Conjugated

Types of vaccines that produce a cellular response (can replicate)

• Nucleic acids

• Live/attenuated

How does an adjuvant help increase the immune response to inactivated/subunit vaccines

Helps the antigen look more pathogenic and causes a better protective response

Occasional unintended consequences of the T_H2 and humoral responses produced by inactivated vaccines

• Harmful response on second exposure to pathogen

• Issues during inactivation during manufacturing

Mechanisms for adjuvants to help stimulate immunity in inactivated vaccines

• Depot: prevents clearing of Ags

• Particulate: collects Ag to increase innage immune response

• Immunostimulating: more cytokines to make the immune system pay attention

Can live-attenuated vaccines cause clinical signs

No

Pros of live-attenuated vaccines

The cell makes the Ag which is then presented on MHC I for complete B and T cell response

Cons of live-attenuated vaccines

• Can convert back if too active

• Not very effective if too inactive

Ways to attenuate a live vaccine

• Culture in cell lines and allow it to weaken through generations

• Incubation in a heterologous host

• Genetic engineering

Vector vaccine mechanism

Pathogenic DNA is inserted into a virus the immune system already recognizes

Expressed end product from a vector vaccine

Virus-like particle

Cons of vector viruses

• Not cost effective

• Stability is not possible for every virus

DNA vaccine mechanism

Host produces foreign antigen as an endogenous antigen

Why does a DNA vaccine need adjuvants

Memory is low because it causes low inflammation

Routes of vaccine administration

• SQ

• IM

• IN

• Aerosolized

• Ingested

Which type of vaccine route creates good mucosal immunity

Intranasal

Reasons for vaccine failure

• Poor handling

• Poor compliance

• Wrong dosing

• Wrong timing

• Poor animal response

• Wrong strain of disease

• Manufacturing error (rare)

When do vaccine reactions happen

Handling errors or hypersensitive animals

Herd immunity

The more individuals that are vaccinated, the less incidence and spread in a population

Factors that influence level and duration of vaccine protection

• Maternal Ab

• Age

• Pregnancy