Vaccination and Epidemiology (Lecture 6 & 7)

example of an inactivated vaccine

eastern equine encephalomyelitis

what are adjuvants

agents used to enhance the immunologic response to inactivated vaccines

how do adjuvants work?

o They cause a slower release and degradation of antigens and stimulate phagocytosis

o Aluminum hydroxide is one widely used adjuvant but other products such as Iscoms are also used

Iscoms= immune stimulating complexes

why does the live attenuated vaccine have better immunogens?

Better immunogens because the modified live virus replicates in the host this producing longer lasting immunity similar to that of a natural infection

how is a marker vaccine created?

1. removing a gene that is not essential for virus replication that induce an antigenic response that is not important in providing protection

2. attenuating the vaccine by removing the thymidine kinase (TK) gene (i.e. two genes are deleted)

example of a live attenuated vaccine

Canine distemper vaccine

what are the disadvantages of attenuated vaccines?

Possible reversion to virulence

Possible spread to in contact animals and fetus

Possible contaminating viruses or mycoplasmas

May not be attenuated for all species

• Example - Canine distemper vaccine

what are the advantages of attenuated vaccines?

Single dose may be effective

Can be given by a natural route stimulating local and systemic immunity

Produces long lived immunity

Inexpensive

what are some disadvantages of inactivated (killed virus) vaccines?

• Multiple doses often required to protect

• No local immunity or interferon produced

• High concentration of antigen causes them to be expensive

• Immunity often short lived

• Any non-inactivated virus can cause disease

what are some advantages of inactivated (killed virus) vaccines

• Stability

• No danger of spread

• No problem with viral interference

• Fatal viruses can be controlled

formite

an object carrying infectious agents and hence transferring them from one individual to another.

nosocomial

(of a disease) originating in a hospital.

latrogenic

caused by treatment (caused by doctor)

Identify the five mechanisms for ensuring the perpetuation of a virus

1. Replicate rapidly and at a high titer in acute self-limiting infections.

2. Shed for long periods of time in persistent/latent infections.

3. Capacity to survive in the environment through resistance.

4. Capacity to be transmitted by a biological agent via perpetuation through a host.

5. Capacity to be transmitted vertically through congenital transmission.

describe acute self-limiting infection

o High efficiency of transmission (many individuals infected over a short time)

o Virus excretion of short duration to limit reduction of susceptible hosts (no latent infections)

o Immunity forces variants; through antigenic drift and shift. (These mechanisms allow the virus to evade the immune response)

antigenic shifts result from 3 mechanisms

1. genetic reassortment between subtypes,

2. the direct transfer of a whole virus from one host species into another, or

3. the re-emergence of a virus that was found previously in a species but is no longer in circulation

describe resistance of the virus to the environment as it relates to virus perpetuation

o Survival favors fomite transmission or transmission in meat products

o Virus is not highly infectious; hence number of susceptible animals does not fall as animals born compensate for those infected

o Equine warts: papilloma virus transmitted by sharing riding bit

o African swine fever virus in smoked (not cooked) salami

How does the virus replicate in an arthropod during biological transmission?

The virus initially replicates in the insect gut after ingestion and then spreads to the salivary gland over several days during the extrinsic incubation period.

What is the extrinsic incubation period, and what factors influence it?

the time it takes for a virus to replicate and spread from the insect gut to the salivary gland. It varies with different viruses and is influenced by ambient temperature.

describe perpetuation of a virus through congenital/vertical transmission

o Virus may be transmitted trans- placentally without necessarily causing either death or fetal abnormalities. Virus may be recognized as "self" i.e. immune tolerance.

o Virus can be transferred through milk

o Viral genome may be integrated into the genome of the gametes (occurs only in poultry as far as we know)

Example: CAE- caprine arthritis encephalopathy= a lentivirus in the retroviridae family

Give an example of a virus that has jumped species but is not zoonotic?

Equine influenza virus has jumped to dogs but is not known to cause infection in humans.

When might the entire viral genome be sequenced in molecular epidemiology?

The entire viral genome may be sequenced when the pathogen is novel, such as canine influenza.

What is an example of sequencing used in epidemiology?

The nucleotide sequences of the VP1 (virus protein 1) genes of foot-and-mouth disease virus, type O, have been analyzed from isolates around the world.

most vaccines on the market are either ____________ or ______________

inactivated or live attenuated

what is an inactivated vaccine?

killed virus

what is a live attenuated vaccine?

1) Uses live weekend microbes (mutated microbes), which more closely mimics the actual infection.

2) Lifelong immunity is often achieved with 1-2 booster vaccines.

Ex: MMR, TB, Chickenpox

what type of vaccine is traditionally the most successful?

live attenuated vaccines

_______________ and _______________ represent sophisticated live attenuated vaccines

Gene deleted and marker vaccines

Reasons why vaccines fail to protect

o Improper use

o Genetic differences between animals

o Antigenic differences (vaccine strain not closely related to field strain)

o Blocking by maternal antibodies

o Administration following infection (Rabies excepted)

what happens when an animal is vaccinated with a marker vaccine?

- the virus replicates and the animal produces protective antibodies to the antigenic proteins coded by the genome

- BUT no antibodies are produced for the gene removed in the vaccinated animal because the gene is absent and thus not coding for the protein

what is the significance of a marker vaccine?

- allows you to tell the difference between an animal that has been vaccinated and one that has the infection

- the vaccinated animal with lack a specific antibody that is typically produced in response to a specific gene (which is removed in the marker vaccine), giving it a negative ELISA test result

- whereas a naturally infected animal will have the gene and associated antibodies which can be detected through an ELISA test

give an example of a vaccine that uses recombinant virus vector from unrelated species

canarypox for ferret canine distemper (CDV) vaccine

describe recombinant pox vaccines

Recombinant pox vaccines combine the safety and stability of attenuated poxviruses with the power of genetic engineering. They safely deliver antigens from target pathogens into the body, mimicking a natural infection and triggering a strong, protective immune response. Their large genome capacity, non-replicating nature, and ability to induce both antibody and T-cell responses make them versatile tools for combating infectious diseases, emerging pathogens, and even cancers.

what are characteristics of an ideal vaccine?

• provides broad-spectrum protection against all isolates of the virus in all the affected species, preventing virus carriage and the possibility of shedding and transmission

• stimulates the level of immunity necessary to drive effective and long-lasting immune responses

• inexpensive to manufacture and simple to administer (oral in some situations e.g. wildlife);

• in the case of live attenuated vaccines, reversion to virulence has to be avoided

• has a long shelf life and is heat stable

• allows discrimination between infected and vaccinated animals (DIVA)

• if used in the dam to protect the newborn, provides strong levels of maternal immunity

• can overcome colostral immunity

• if adjuvanted, does not induce cancer

what does DIVA stand for?

differentiation of infected from vaccinated animals

Epidemiology

study of the determinants, dynamics; and distribution of diseases in a population

examples of horizontal transmission

o Direct Contact

Licking, rubbing, biting, sexual acts

o Indirect Contact

Fomites, such as bedding, instruments, halters, grooming equipment

o Common Vehicle

Virus contaminated meat, water supplies

o Airborne

Droplet, aerosol, dander

o Arthropod Borne

Mechanical and biological

examples of vertical transmission

o Intra-uterine

o Milk

o Integration proviral DNA into germ line of fertilized egg (not in mammals)

Zoonotic Infections

Diseases transmitted from animals to humans

antigenic drift

- point mutation that allows immune escape

- point mutation that allows infection of a new host species

parvovirus, started in cats and then mutated slightly to now infect dogs

example of antigenic drift

antigenic shift

- An abrupt change in the subtypes found in host species

- genetic reassortment between viruses results in major antigenic change

describe persistent/latent infection

o Prolonged period of excretion reduces the population necessary for transmission (animals born/introduced compensate for those infected)

o Promotes transmission for non-herding species by venereal route

o Antibody and virus can co-exist (mostly allowing the animal to be protected from disease but remaining potentially infectious)

Cow with infectious bovine rhinotracheitis (IBR): a herpes infection

describe virus perpetuation through a host

o Vector host is often an arthropod in which virus replicates.

o Infection in the arthropod is persistent and, in some cases, virus can be passed vertically

o There may be several animal hosts and several arthropod vectors

o Biological transmission indicates the virus replicates in the arthropod, compare mechanical transmission through contaminated mouthparts

Example: west nile encephalitis transmitted by mosquitoes

What is biological transmission?

involves the replication of a virus within an arthropod vector, which acquires the virus by feeding on the blood of a viremic animal.

How is the virus transmitted to animal hosts in biological transmission?

Virions present in the salivary secretions of the vector are injected into animal hosts during blood meals.

How does arthropod transmission enable a virus to cross species barriers?

the same arthropod can bite birds, reptiles, and mammals that rarely or never come into contact in nature

What role does wildlife play in the perpetuation of viruses?

Wildlife often plays a significant role in the perpetuation of viruses, especially Emerging Infectious Diseases (EIDs), which can include zoonotic viruses present in many virus families.

What are Emerging Infectious Diseases (EIDs)?

diseases caused by pathogens, including zoonotic viruses, that have recently appeared or increased in incidence and are often associated with wildlife

What does it mean for a virus to "jump species"?

"Jumping species" refers to a virus's ability to maintain a line of transmission in a new species, even if it is not synonymous with being zoonotic.

Is "jumping species" the same as being zoonotic? Why or why not?

No, "jumping species" is not the same as being zoonotic. For example, equine influenza virus has "jumped" to dogs but is not known to cause infection in humans

give examples of some factors that affect survival of viruses in the environment

• Seasonal variations

o Arbovirus diseases are often seasonal

o Some viruses survive better as aerosols in a humid climate

• Housing and management

o Dog shows

o Calves going to feedlots

o Retreat to wildlife reservoirs

o Migrating birds

Primary host

- the host from which the adult parasite gets its nourishment and in which sexual reproduction occurs

- natural host, long term

Reservoir host

- The organism that becomes infected by a pathogen and serves as a source of transfer of the pathogen to others

- Also primary/maintenance host, can be infected wildlife that serve as sources of infection to domestic animals.

Dead End/Incidental host

host is severely infected, but the level of viremia is too low for blood sucking vector to pick up the virus.

An integrated approach to disease control is through:

• Using vaccines

• Use of Molecular Epidemiology and genomic sequencing

• Modeling

• Using surveillance

• Staying informed via websites that monitor disease occurrence and outbreaks

goals of immunization/vaccination

Eradication or elimination of disease

Reductions in severity of disease

Prevention of outbreaks/epidemics

Community immunity aka herd immunity

Slows down the spread of a disease or eliminates the spread altogether

Protects those that cannot be vaccinated

Smallpox, polio, measles, rinderpest

Useful in "self-limiting" infection without long-term consequences- influenza example in people

What is molecular epidemiology?

the use of molecular biological methods for the epidemiological investigation of viral diseases

How does sequencing contribute to molecular epidemiology?

Sequencing allows for the identification of viral strains with greater specificity than serological methods and can be used to sequence entire viral genomes, especially for novel pathogens like canine influenza.

How are big data and simple models used in molecular epidemiology?

big data and simple models are utilized to track the spread of infections and better understand their epidemiology.

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