Lecture 6: Prophylaxis and therapy of viral infections Flashcards
What is important to note about vaccination plans?
You need to make your own. Dont rely on others.
Who created the first vaccine? How?
Edward jenner -> Cowpox for small poxs
What are the categories of protection from viruses?
- Interferons and interferon inducers
- Viral vaccines
- Chemotherapeutic agents
What are the 3 categories of vaccines?
I -First generation (conventional vaccines)
II-Second generation vaccines
III-Third generation vaccines
What kinds of vaccines are part of First generational / conventional vaccines?
- Live attenuated vaccines
- Heterologous viral vaccines
- Inactivated viral vaccines
What kinds of vaccines are part of Second generation vaccines?
- Subunit vaccines
- Genetically engineered vaccines
What kinds of vaccines are part of third generation vaccines?
DNA vaccine
Are emergency vaccines for infected animals?
No they are for at risk animals, not infected animals.
What are the purposes of vaccinating? What time frame should you be vaccinating for :?
- To render the virus non infectious without destroying its antigenicity/immunogenicity
- Prophylaxis: vaccine is given to animals to protect them against some expected viral diseases
- Protection of newborn animals: pregnant animals are vaccinated to transfer the passive immunity to their offspring
- Vaccines must be given in advance before expected infections with reasonable time to allow the immunity to develop ( takes 1-2 weeks to develop an immune response)
- Vaccines may be administered during an outbreak with some viral infections in an attempt to protect the non infected animals at risk
What is the criteria for an ideal vaccine?
- Produce some kinds of solid immunity (long lasting)
- Produce an early protective immunity
- Provides protection against pathogen variants
- Produce a life long immunity preferably in a single dose
- Prevents infection
- Do not produce any carrier state in vaccinated animals
- Can be administered by mass immunization • Safe and stable
- None or minimal side effects in the vaccinated animals ( enough to stimulate immune system but not enough to debilitate animal)
- To be fit for a long term storage vaccine banks
- Thermostable to avoid cold chain
- Differentiation between infected and vaccinated individuals (DIVA)
- Cost Effective
- Produced inexpensively and in large quantities
What is DIVA?
A system to tell if an antibody is via natural infection vs. vaccination. A marker is applied to a component in a vaccine so you can tell if the patients antibodies are via vaccine.
What is an attenuated vaccine?
Vaccine made less virulent
What is a killed vaccine?
Vaccine of a killed virus, this will still stimulate the immune system.
What vaccine is the most ideal?
Killed vaccines
What is a subunit vaccine?
Nonrecombinant purified part of virus
What is the benefit of a clone vaccine?
You can make a competent viral vector vaccine, DNA vaccine, or use proteins to make a virus like particle vaccine vs. a subunit vaccine
What is the types of active immunity? Passive immunity?
Active:
- Natural infection
- Vaccination
Passive:
- Maternal immunity
- Hyperimmune sera
What are the requirements to develop protective immunity against viral infection?
- IgG, IgA, CTL
Where can you find IgA?
- Submucosa, vagina, digestive tract, ect ( bodily secretions)
What is the primary protective immunity?
- Abs in the blood (IgG) immune
- IgA (mucosal surfaces)
- Cell-mediated immunity (Tc)
What is the systemic infection protective immunity? *** mean the magnitude of each
- IgA*, IgG***, Tc ***
What is the local infection protective immunity? *** mean the magnitude of each
- IgA***,Tc***, IgG*
What are the important considerations for a vaccine?
Design parameters, safety and efficacy, practical considerations.
What are the practical considerations for a vaccine?
Economical/Ease in handling
• Multivalent, one-shot
• Low cost of production
• Stable
• Needle-free delivery
What are the design parameters to be considered for a vaccine?
• Clear understanding of pathogenesis
of the target virus
• Consider characteristics of the virus for selection of vaccine type and delivery route
• Cellular vs humoral immunity, or both
• Mucosal vs parenteral vaccination or both
• 90% of all viruses enter through
mucosal surfaces
What are the safety and efficacy considerations for vaccines?
• Effective in newborn animals
• Minimal adverse reactions
• Minimal tissue damage
• Safety in pregnant animals
• Induction of both humoral &
cellular immunity
• Mucosal immunity
• Long-term memory
What are the principles of a live attenuated vaccine?
Weakened viruses under lab conditions.
They will grow in a vaccinated individual but because they are weak they will cause no or very mild form of the disease,
What are some examples of attenuated vaccines?
- Oral polio vaccine (OPV)
- Measles
- Rotavirus,
- Yellow fever
What are side effects of live attenuated vaccines?
Revert to virulence and causing the original form of diseases of the wild type virus in some cases
• Potential harms to the immunocompromised personnel
• Contaminated cell culture vaccines: Rota virus and Measles virus if grow in cell culture
• Not recommended in case of pregnancy
What immune response occurs with live attenuated vaccines?
- Stimulates the production of excellent immune response. ( Humoral + CMI) similar to wild type virus
Stimulates production of memory cells
How do they grow live attenuated vaccines so that it can be controlled?
Passage the wild type virus in a unnatural host
• Passage of the wild type virus in unusual conditions
How does passage of the wild type virus in an unnatural host affect the vaccine?
By continued passage of the wild type virus in unnatural host- progressive adaptive mutations - virus adapts to new host- retain their capacity for transient growth within an inoculated natural host.
How does growing a pathogenic virus under abnormal culture conditions affect the vaccine?
– By growing a pathogenic virus for prolonged period under abnormal culture condition- select mutants better suited to growth in the abnormal culture conditions and less capable of growth in the natural host.
What are the advantages of live attenuated vaccines?
What are the disadvantages of live attenuated vaccines?
What are examples of live attenuated veterinary vaccines and where they were created?
• Canine parvovirus (CPV): feline kidney cells
- Feline herpesvirus (FHV): feline kidney cells
- Infectious laryngotracheitis virus (ILT): chicken kidney cells, embryonated chicken eggs
What are heterologous viral vaccines? What are some examples?
• Principles: two viruses that are antigenically related to each others thus protection arise from the presence of
the cross reacting antigens
• The heterologous vaccines are naturally attenuated
• Examples of heterologous vaccines
-Pigeon poxvirus protects against Fowl poxvirus
- Shop fibroma virus rabbit protects against Rabbit myxomatosis
- Sheep-pox virus protects against Lumpy skin diseases virus (LSDV)
- Herpesvirus of turkeys (HVT) protects against Marek’s diseases virus (MDV)
- Rinderpest virus (RPV) and measles virus protects against Canine distemper virus (CDV)
What are inactivated or killed viruses? What are the methods of killing the virus?
Whole virus inactivated or propogated via physical or chemical methods.
Physical methods: Formalin, Heat, beta propiolactone
Chemical methods: UV, irradiation.
• Virus does not replicate in the vaccinated animals requires a larger
antigenic mass
- Va c c i n e may be expensive to produce
- Requires an adjuvant to enhance the magnitude of the immune response
What are the advantages of inactivated/ killed vaccines? How do they work?
These agents inactivate the viral nucleic acids without affecting the capsid or envelope proteins against
them the antibodies are produced
- They are relatively stable, safer especially in pregnant animals, minimal post vaccine rxns, possibility of spread is rare.
What are the diadvantages of inactivated/ killed vaccines?
- very expensive ( made from highly concentrated virus)
- short term immunity, needs booster doses
- less efficient in induction of CMI
What are the kinds of Adjuvunts and their modes of action?
Depot adjuvant: Causing depot formation at the site of injection - For example, mineral compounds, oil-based adjuvants, liposomes
- Particulate adjuvant: Acting as delivery vehiclesfor the antigens, which may help in targeting antigens to immune
- Immuno-stimulatory adjuvant: ISCOMs: are 40 nm large particles made up of saponins (Quil A), lipids, cholesterol and antigen, held together by hydrophobic interactions between the first three components
- Freund, in 1937, demonstrated the adjuvant effect of mineral (paraffin) oil mixed with killed Mycobacteria, referred to as Freund’s complete adjuvant (FCA).
- The water-in-oil emulsion without Mycobacteria, known as Freund’s incomplete adjuvant (FIA), has been used in a number of veterinary vaccines.
Wah is an adjuvant?
Def: a component that potentiates the immune
response to an antigen and/or modulates it
towards the desired immune response.
What are the effects of an adjuvant on the immunogenicity of viral vaccines?
How are inactivated vaccines administered and what immune response does it have in each location?
Inactivated vaccines (parenteral route):
- Administered I/M or subcutaneous routes only
- Generates IgG only,
- no cellular immunity –
- protective immunity for systemic infections associated with viremia; to lesser extent local infections.
How are live vaccines administered and what immune response does it have in each location?
Live vaccines:
• Administered in the mucosal surfaces (Intranasal, oral or genital)
▪ IgA (mucosal immunity), IgG, cytotoxic T cells Protective immunity for both systemic and local infections
• Administered by parenteral routes (I/M, sub cut)
▪ IgG and Tc but no IgA
What is the main difference between live virus and killed virus vaccines in terms of immunity?
Live virus: one dose can be protective) amplification of injected dose occurs)
Killed virus: Multiple doses are necessary for protection
What are the Common disadvantages of the conventional viral vaccines?
- Reversion to virulence
- Incomplete inactivation
- Contaminations
- Secondary effects
- Inflammation, granuloma, fever, hypersensitivity
- Immuno-suppression
- Inability to differentiate vaccinated from infected animals
- Cold-chain requirement
What are subunit vaccines? What is an example of this?
Split virus products: viral proteins separated from virus-infected cells via mechanical or chemical treatment
What are the types of recombinant vaccines and how do they work?
What is the advantages of a subunit vaccine?
- Prepared from virus components devoid from viral NA such as capsid and envelop proteins
- These components are responsible for the induction of the immune response against the virus of concern
• Advantages of the subunit vaccines
- It is safe because it is free from NA -It does not induce febrile reactions which induced by some proteins in the other viruses -It is highly immunogenic in high doses
What is a genetically engineered subunit vaccine (single gene)?
- Virally vectored subunit vaccine
- Plasmid based/vectored subunit vaccine
- expressed in bacteria
- expressed in yeast and mammalian cells
What are DNA Vaccines?
These vaccines are based on the introduction of a DNA plasmid into the host cells The plasmid carries a protein-coding gene that transfects cells in vivo at very low efficiency and expresses an antigen that causes an immune response.
What are the delivery methods of DNA vaccines?
• Injection of the prepared DNA vaccine in saline solution
- Intramuscular (IM)
- Intradermal (ID)
-May be assisted by the electroporation method
• Gene gun delivery approach
What are the advantages of DNA vaccines?
What are the disadvantages of DNA vaccines?
What is the distribution of protective immune response in vaccinated animal populations
Usually occurs as a bell curve. No vaccine is expected to produce 100% protection
What is maternal immunity? How long do serum IgG antibodys last in young animals?
• Maternal immunity
- passive transfer of humoral immunity via colostrum/milk/egg yolk
- protection of newborn and young animals
- prevention of enteric infections
- No cellular immunity and lacks memory immune cells.
• Example:
-Transmissible gastroenteritis virus (TGEV) infection of pigs. -Corona and Rotavirus infections in calves.
• Vaccination of young animals: Serum IgG antibodies persist for : - up to 6 months in cattle, horses
- up to 4 months in dogs, cats, pigs
- up to 1 month in chickens, turkeys
What are ways we can overcome the effects of maternal antibodies? Why do we need to do this?
- To do repeated vaccinations before the predicted loss of antibody
- Using the intranasal route (mucosal) when modified live vaccines are used
We do this because maternal antibodies interfere with immunization of young animals.
What are some causes of vaccine failure?
- Wrong strain/serotype of organisms
- Method of production destroy protective epitopes - inactivated vaccines
• Failure of an effective vaccine to stimulate protective immunity may be due to:
1. Unsatisfactory administration
- A live vaccine may have died
- Timing - Vaccination Schedules - Lag time
- Animal to animal variability
What can cause vaccine reactions and what reactions can you see?
What is a ring vaccine strategy?
• The vaccination of all susceptible herds in
a prescribed area around an outbreak of
an infectious disease
• Ring vaccination controls an outbreak by
vaccinating and monitoring a ring of
herds around each infected herd
• The idea is to form a buffer zone of
immune herds to prevent the spread of the
disease
What is heard immunity?
• Herd immunity is achieved when large number of individuals become immune against circulating infectious diseases
- Herd immunity restrict the spread from person to person
- Herd immunity can be achieved when Large number of community either recovered from infection or vaccinated against certain infectious diseases
• In some research, herd immunity may be achieved if up to 70% of the population are immune (recovered/vaccinated)
What occurs during the typical human/ animal vaccine pipline?
What are some SARs-CoV- 2 vaccine candidates?
What is the design of some SARS-CoV-2 mRNA vaccines?
How does the pfizer- biotech covid 19 vaccine work/ mechanism of action?
What is the immune response to Sars Cov-2 mrna vaccines?
What are some common challenges in the veterinary vaccine sector?
• Cost Effectiveness economy of vaccine production
• Diseases where vaccine is most demanding - Classical swine fever, sheep and goat-pox,
bluetongue, FMD, EHV-1/4, strangles, haemorrhagic septicemia (HS), etc
- Vaccine updating: many RNA viruses (FMD virus, bluetongue virus, and influenza viruses) are highly variable and require updating of vaccine very frequently
- Potency Testing batch potency tests - involve administration of vaccine to target species or laboratory animals
• Viruses with genetic heterogeneity, high mutation rates and quasi-species are difficult targets for
vaccination: porcine respiratory and reproductive syndrome virus (PRRSV), Retroviruses, bovine viral
diarrhea virus (BVDV)
•Cellular immunity and long-term memory often difficult to be achieved
