Test 3 - Chapter 11 - Vaccination
Which type of vaccine is expected to best mimic a natural infection and produce the longest-lasting immunity
Live-attenuated vaccines most closely mimic a natural infection because the organism can infect cells and replicate in the body as the natural pathogen would. Live-attenuated vaccines therefore typically produce the strongest and longest-lasting immunity. Killed vaccines and subunit vaccines cannot cause infection and therefore do not as effectively mimic a natural infection.
2 types of Covid vaccines available in the US?
mRNA vaccines and viral vector vaccines
Herd Immunity 1) What is herd immunity? 2) How does it protect non-immune individuals? 3) Chains of infection are...? 4) Decreased vaccination rates cause a loss of...?
1) a large majority of immune individuals protect a small minority of non-immune individuals 2) There is a smaller probability that non-immune individuals will encounter the pathogen. 3) disrupted 4) herd immunity
Killed and live-attenuated vaccines are available for Polio virus and each has benefits and drawbacks that must be balanced 1) Polio has been eradicated in most countries but remains endemic in...? 2) What two types of vaccines are available for polio? 3) Killed/Inactivated vaccine protects an individual, but does not...? 4) Oral, live-attenuated vaccine prevents...? (a) What's the risk with this one? 5) What kind of vaccine is recommended in countries where the risk of infection remains high?
1) Afghanistan & Pakistan 2) 2 vaccines: live-attenuated and killed/inactivated 3) prevent transmission 4) person-person transmission (a) However, the live-attenuated pathogen can occasionally mutate back to a pathogenic form in certain conditions. 5) Live-attenuated vaccine
Vaccination 1) What is a vaccination? 2) What is the goal? 3) What was the first medically prescribed vaccine? (a) What did it result in?
1) Deliberate delivery of pathogen antigens that can elicit a primary immune response but have little pathogenic potential. 2) The goal is the development of long-lasting immunological memory. If an individual encounters the pathogen, they will hopefully be able to respond to it with a strong memory response. 3) The first medically prescribed vaccine was against Smallpox (a) Resulted in the global eradication of Smallpox in 1979
Subunit vaccines 1) What do subunit vaccines contain? 2) Subunit vaccines may also need to contain a...? (a) What is it? (b) Why might it need to be included?
1) Do not contain whole cells; contain only antigens that best stimulate the immune system 2) Subunit vaccines may need to contain an adjuvant (a) A substance that stimulates the innate immune system (b) Because the subunit alone may not be not contain PAMPs to activate an innate immune response and activate dendritic cells
Live-attenuated pathogens versus killed/inactivated pathogens 1) How are live-attenuated pathogens produced? (a) What happens to the pathogen over time? (b) These typically elicit the strongest...? (c) Can they still cause infection? 2) Killed/inactivated pathogens are unable to...? (a) What kind of response do they elicit and why?
1) Live-attenuated pathogen is produced by growing in cells from another species (a) Becomes less able to grow in human cells causing reduced pathogenicity (b) memory responses (c) They can still cause an infection but it is rapidly cleared before it can cause disease because it is no longer well adapted to infecting humans 2) replicate and cause infection (a) Typically elicit a weaker memory response that live-attenuated vaccines because they don't as effectively mimic a natural infection
Current COVID vaccines in the US 1) Who makes mRNA vaccines? 2) How do mRNA vaccines work? (a) What are they similar to? 3) Who makes the viral vector vaccines? 4) How do viral vector vaccines work? (a) What are they similar to?
1) Pfizer and Moderna 2) They deliver mRNA encoding the spike protein from the COVID-19 virus. In the body, the mRNA is translated into the COVID-19 spike protein, and an immune response is generated against the spike protein. (a) Similar to a subunit vaccine only using mRNA encoding the subunit 3) Johnson & Johnson 4) Uses a different virus (a non-pathogenic virus that does not cause disease) to infect cells and deliver DNA encoding the spike protein from the COVID-19 virus. An immune response is generated against the spike protein. (a) Similar to a subunit vaccine only using a viral vector to deliver DNA encoding the subunit
Smallpox vaccine 1) What was variolation? (a) What was the goal? (b) How many people did this still kill? 2) What happened in the early 19th century? 3) What has happened since the 20th centuries?
1) Prior to the 19th century, variolation was the practice of immunization using dried material from the pustule of a mild Smallpox infection (a) The goal was to get a mild smallpox infection rather than risk a serious one that might be more fatal (b) This still killed about 1 in 100 individuals it was performed on. 2) In the early 19th century, the related Cowpox virus was used as a vaccine for Smallpox. 3) Since the 20th century, the related Vaccina virus was used in the vaccine against Smallpox.
What is a conjugate vaccine and why is it necessary to use a conjugate vaccine to vaccinate infants against encapsulated pathogens?
A conjugate vaccine is used to enable infants to produce an antibody response for a carbohydrate antigen present in a bacterial capsule to provide antibody protection against an encapsulated pathogen. Typically, a thymus-independent type 2 (TI-2) response is first produced in response to an encapsulated pathogen. However, children under age 2 do not produce strong TI-2 responses, so an infant would not produce a response to the polysaccharide antigen alone. A conjugate vaccine enables a thymus dependent B-2 cell response to be produced to provide protection. The conjugate vaccine consists of a polysaccharide antigen (from a bacterial capsule) linked to a protein antigen. The structure is taken up by B-2 cells with a receptor that binds to the carbohydrate antigen, and the peptides from the protein are then presented to T-cells. The B-cell is then activated to produce antibodies specific for the carbohydrate antigen.
What is an adjuvant, and in which type of vaccine may it be necessary?
An adjuvant is a component that may need to be added to a subunit vaccine to activate the innate immune response. During an infection, as discussed in the first part of the course, the innate immune response is activated by PAMPs binding to PRRs. For example, macrophages must recognize PAMPs in order to produce an inflammatory immune response (with cytokines subsequently shaping the nature of the adaptive response), and immature dendritic cells become activated by PAMPs to upregulate co-stimulatory molecules and MHC molecules (both signals are required to subsequently activate T-cells). Therefore, an innate immune response is a prerequisite to the initiation of a primary adaptive immune response. A purified antigen used in a subunit vaccine may not contain any PAMPs. An adjuvant is a molecule that is added that can stimulate an innate immune response- it either contains microbial components that provide natural PAMPs or a chemical that can mimic a PAMP)
Why is the immunological memory against small pox so long lasting?
Because smallpox is a DNA virus, the rate of change is very slow so immunological memory is long-lasting. There are also no animal reservoirs for smallpox to mutate in since it only affects humans.
Vaccines must be perceived to have benefits that outweigh risks
Examples ❑ Polio vaccine ▪ Live-attenuated vaccine is preferred in high-risk countries, but inactivated vaccine is preferred in low-risk countries. ❑ B. Pertussis vaccine (protects against whooping cough) ▪ Killed whole-cell Pertussis vaccine caused pain, swelling, fever & occasionally short-lived neurological signs ▪ An acellular vaccine (subunit vaccine) is now used with fewer adverse side effects ❑ Smallpox vaccine ▪ Caused serious side-effects in ~ 1 in every 1 million vaccines ❑ Perceived side effects can be harmful to society ▪ A retracted research paper in late 90s suggesting a link between measles and autism led to reduced rate of measles vaccination in some countries. ▪ Unsubstantiated claims linking B. Pertussis vaccine to brain damage in the 1970s (which was not shown to be linked to the vaccine) led to reduced rate of B. Pertussis vaccination.
How does polio enter and where do it go?
It enters through the mucosal surfaces and then moves to the neurons
How lethal was smallpox?
It killed about 30% of individuals infected with it.
What type of vaccination typically elicits the strongest memory responses?
Live-attenuated pathogen vaccines
What is herd immunity, and why is it important?
The majority of vaccinated individuals protect the minority of unvaccinated individuals by reducing the chances that an unvaccinated individual will encounter an infected person. As herd immunity decreases, there is more opportunity for a chain of transmission to be maintained because there is increased likelihood that an infected individual will come into contact with an unvaccinated individual. Strong herd immunity is important to give protection to vulnerable people, such as newborn babies, unvaccinated children and those too sick to be vaccinated
How are live-attenuated pathogens produced?
To date, live-attenuated pathogens have been produced by growing the pathogen in cells that are not human cells. The pathogen develops mutations that make it better adapted to the cells of another animal, but less well adapted to human cells, therefore decreasing the ability to cause disease in humans.
What is vaccination and why is it performed?
Vaccination is the deliberate immunization of an individual with pathogen antigens that can produce a primary immune response but have minimal potential (if any) to cause disease symptoms. It is performed to generate immunological memory, so if an immunized individual encounters the natural pathogen, the immune system will be able to respond with a faster, more effective memory/secondary immune response.
What are: a) live-attenuated vaccines, b) killed/inactivated vaccines and c) subunit vaccines?
a) Live-attenuated vaccines use a live form of the pathogen that has been modified to make it less virulent. It still retains the ability to infect cells and replicate and cause a primary infection, but it causes only a transient, harmless, infection, which is quickly cleared from the body before it causes disease. b) Inactivated vaccines, also called killed vaccines, use a whole pathogen (virus or bacterial cells) that have been inactivated (i.e., 'killed') with chemical or physical treatments. The inactivated/killed don't have the ability to replicate in the body and cause infection, but a primary immune response is still generated against the pathogen antigens. c) Subunit vaccines do not use whole cells; they use only select antigens of a pathogen. They are unable to replicate in the body and cause infection, but a primary immune response is still generated against the pathogen antigens.
