lect 10 - vax

Which 2 features of the adaptive immune response do vaccines use?

Specificity and memory.

What is the main challenge in vaccine design?

Delivering the pathogen or its antigens without causing disease, while still triggering an immune response.

Besides being immunogenic, what else must a vaccine do?

Trigger the appropriate type of immune response for that pathogen.

What are the 6 qualities of a good vaccine?

Safe, protective, durable, appropriate immunity, practical, and disease-control value.

What does “safe” mean for a vaccine?

An acceptable risk in the intended species, age and health status.

What does “protective” mean for a vaccine?

A clinically meaningful reduction in infection, disease, transmission or production loss.

What does “durable” mean for a vaccine?

Protection lasts for a useful period.

What does “appropriate immunity” mean for a vaccine?

It produces the antibody and cellular responses that particular pathogen requires.

What does “practical” mean for a vaccine?

It works with field administration, storage, cost and vaccination schedules.

What does “disease-control value” mean for a vaccine?

It may support fetal protection, herd immunity or DIVA (telling infected animals apart from vaccinated ones).

How long does passive immunization last compared with active?

Passive is transient (it wanes); active lasts much longer (years).

What happens to heterologous immunoglobulin (Ig from another species)?

It wanes quickly, and repeated doses can cause serum sickness.

Why does Ig from another species wane faster than Ig from the same species?

The body recognizes it as foreign and clears it. Ig from the same species (homologous) lasts longer.

What is a benefit of passive transfer of maternal antibody?

It protects neonates

What is a drawback of maternal antibody?

It can interfere with active immunization (vaccinating the young animal).

What are the 4 types of non-live vaccines?

Killed/inactivated, recombinant protein/subunit, DNA/RNA and conjugate.

How are killed/inactivated vaccines made?

The pathogen is inactivated with heat, formalin or another chemical treatment.

What is a recombinant protein/subunit vaccine?

Specific antigens are expressed and purified, or the pathogen is inactivated, disrupted and at least partly purified.

How do DNA/RNA vaccines work?

A plasmid or mRNA that encodes the antigen makes the host express the protein after immunization

What is a conjugate vaccine?

A poor immunogen attached to a strong immunogen (a hapten–carrier).

What are the 2 types of live vaccines?

Attenuated and vectored.

What is an attenuated vaccine?

The pathogen is weakened on purpose or by trial and error, or a related virus from another species is used to give immunity without disease.

What is a vectored vaccine?

An attenuated virus or bacterium encodes the antigen and expresses it after immunization/infection (for example, a recombinant virus-vectored vaccine).

What is a split vaccine?

The pathogen is grown, killed, then disrupted, and the antigen is enriched.

What is a subunit vaccine?

Specific antigens are purified from the pathogen, or expressed and purified (a recombinant subunit).

How is a recombinant subunit vaccine made?

The gene for the antigen is cloned into another organism (such as a bacterium), which produces large amounts of the protein to purify.

What are the 4 types of non-replicating virus vaccine shown on slide 11?

Whole inactivated virus, split virus, subunit and recombinant subunit.

How does a DNA vaccine produce antigen?

The host’s own cells make the antigen from an administered plasmid.

What type of immunity can DNA vaccines stimulate?

Both antibody and cellular immunity.

What are the manufacturing advantages of DNA vaccines?

They are rapid and potentially inexpensive to design and make.

What is a limitation of DNA vaccines across species?

Immunogenicity and delivery vary among species.

What theoretical concerns about DNA vaccines are monitored?

Integration into the host genome and anti-DNA responses.

What features do DNA vaccines combine?

Features of non-living vaccines plus antigen expression inside cells.

Why do DNA vaccines produce endogenous antigens?

The DNA enters host cells and is functional, so the antigen is made inside the cell.

Where is a vaccine’s mRNA translated, and does it enter the nucleus?

It is translated in the cytoplasm and does not enter the nucleus.

What type of immunity can mRNA vaccines stimulate?

Both antibody and cellular immunity.

What is a manufacturing advantage of mRNA vaccines?

They are rapid to design and make.

What determines the reactogenicity, delivery and storage of an mRNA vaccine?

The formulation.

What must be established for each mRNA vaccine product?

its performance and practicality in each species.

What will decide whether mRNA vaccines are adopted in veterinary medicine?

Product performance, cost, storage and delivery.

What is linked together in a conjugate vaccine?

A bacterial polysaccharide covalently linked to an immunogenic protein carrier.

What does conjugation do to the polysaccharide immune response?

It turns a poorly remembered polysaccharide response into a T-dependent response.

What does the carrier protein recruit?

CD4 T-cell help.

What are the steps of a conjugate vaccine response?

1. A polysaccharide-specific B cell binds and takes in the conjugate.
2. Carrier-protein peptides are presented on MHC II.
3. Carrier-specific CD4 T cells help that B cell.
4. The response gains class switching, affinity maturation and memory.

Which gives a good antibody response: hapten alone, carrier alone, or hapten–carrier?

Hapten–carrier. Hapten alone gives a poor response.

What are the pros of killed/non-replicating vaccines?

No residual virulence, and they are generally easy to store and handle.

What are the cons of killed/non-replicating vaccines?

They may need adjuvants, cost more to produce, and may not mimic real infection, so the adjuvant and route become critical.

What is the potential of mRNA vaccines, and their current limitation?

They may combine the best features of live and killed vaccines. Outside pandemic or anti-cancer use their role is uncertain, although an mRNA seasonal influenza vaccine has been licensed.

What is blind attenuation?

Serial passage of a pathogen to drive mutations that weaken it.

What are the steps of serial-passage attenuation?

Isolate the pathogen from a diseased individual → passage it repeatedly in different substrates (cells, eggs, animals) → mutations attenuate it → confirm attenuation in challenge models.

What is cold adaptation?

Growing the pathogen at temperatures below the host’s core body temperature, which weakens its growth in the host. It is rational but still blind attenuation.

What does serial passage select for?

Mutations that reduce replication or virulence in the target host.

Can the attenuating mutations be identified?

Yes, after selection.

What does reversion risk depend on?

The organism, the attenuation mechanism, genetic stability, and the opportunity for replication and transmission.

What are live vaccines evaluated for?

Reversion or increased virulence, when relevant.

What is a rationally attenuated vaccine?

A known virulence determinant is mutated to be non-functional or removed completely, making the pathogen attenuated or avirulent.

Do rationally attenuated vaccines need reversion testing?

Yes, like all attenuated vaccines.

How is a virus-vectored vaccine made?

The gene for the vaccine antigen is inserted into a viral or bacterial vector.

How does a vectored vaccine work in the host?

The vector enters host cells and expresses the antigen.

Does a vector always replicate in the host?

No. Depending on the vector and species it may replicate, replicate poorly or not replicate at all.

What type of immunity does intracellular antigen expression stimulate?

Both antibody and cellular immunity.

Why were DNA viruses used as the first vaccine vectors?

they were the first viruses whose genes could be inserted and removed.

What is vaccinia?

Roughly, the smallpox vaccine virus, which has been widely studied.

Which animal poxviruses are used as vaccine vectors?

Fowlpox and canarypox.

What poxvirus-vectored vaccine helped control wild rabies in Europe?

A poxvirus (vaccinia) expressing the rabies glycoprotein.

What are the benefits of live-attenuated, recombinant and vectored vaccines?

They express antigen inside host cells, mimic important features of infection, generate antibody and cellular immunity, and may need fewer doses than non-replicating protein vaccines.

What are the limitations of live-attenuated, recombinant and vectored vaccines?

Residual virulence, shedding or reversion (for replicating products); pre-existing or vaccine-induced immunity to the vector can reduce performance; and safety, dose, storage and handling requirements are product-specific.

Which vaccines mainly need adjuvants?

Non-live vaccines.

What are the types of adjuvants?

Depot, particulate, immunostimulatory and combinations.

Can adjuvants be used with DNA, live-attenuated or vectored vaccines?

Yes, as recombinant adjuvants.

What is the purpose of adjuvants?

To enhance the immune response triggered by vaccine antigens.

Do vaccine doses scale with body weight?

Usually not. Use the dose, minimum age, schedule and booster interval set for the licensed product.

Which route should you give a vaccine by?

The route on the label.

What does the route of administration influence?

Antigen uptake, innate stimulation, tissue targeting, safety, and mucosal vs. systemic immunity.

What field delivery methods can be used for vaccines?

Intranasal, aerosol, drinking water, feed, immersion and oral bait.

When are field delivery methods useful?

When local immunity or mass administration is important.

What are examples of field vaccine delivery?

Intranasal respiratory vaccines, aerosolized Newcastle disease vaccine (poultry) and oral rabies vaccination of wildlife.

Which agency regulates veterinary vaccines and biologics in the US?

The USDA APHIS Center for Veterinary Biologics (CVB).

What does APHIS license?

Both the manufacturing establishments and the individual products.

What 4 things must be shown for full licensure?

Purity, safety, potency and efficacy.

What does APHIS review for licensure?

Manufacturing and test methods, study data and labeling.

Where must licensed vaccines be made?

At an approved establishment, using methods filed with APHIS.

What document guides the testing of each vaccine serial?

The approved Outline of Production.

What tests may be done on each vaccine serial?

Identity, purity, sterility (freedom from extraneous agents), safety and potency, as applicable.

What independent oversight does APHIS provide?

It may test selected serials itself and inspects facilities, methods and records.

What supports a vaccine’s expiration date and storage conditions?

Stability data.

What supports a vaccine’s approved indication?

Efficacy studies.

When are conditional licenses used?

For an emergency, a limited market, a local situation or another special circumstance.

What safety and purity requirements do conditionally licensed vaccines meet?

The same requirements as fully licensed products.

What efficacy evidence is required for a conditional license?

A reasonable expectation of efficacy, not complete efficacy evidence.

Does a conditionally licensed vaccine need a validated potency test?

Not necessarily. A fully validated potency test may still be in development.

How long does a conditional license last?

Usually 1–2 years. It may be reissued if progress toward full licensure is satisfactory.

Who may need to authorize distribution of a conditionally licensed vaccine?

Individual states.

How can you recognize a conditionally licensed vaccine on its label?

The label states it is conditionally licensed and uses limited wording such as “For vaccination against…”

What 3 ways are used to determine vaccine effectiveness?

Immune measures linked to protection, vaccination–challenge studies and field efficacy trials.

How are lab measures of immunity done?

Animals are vaccinated, samples (such as blood) are collected, and antibody or other immune responses to the vaccine agents are measured.

Which pathogens is antibody especially important against?

Extracellular bacteria and viruses.

Which pathogens is cell-mediated immunity especially important against?

Viruses and intracellular bacteria.

Do lab measures of immunity always predict protection?

No. They don’t always correlate with protection against disease.

What should you check when a study reports lab measures of immunity?

Whether the immune response was the only outcome measured, or whether disease after challenge (or natural disease) was also evaluated.