Viral Vaccines

Question 1

What are the two arms of the immune response? Briefly describe both.

Answer 1

1) Innate immunity: the innate immune system is based on distributed receptors that recognize certain molecular patterns, found in microbes. these receptors are called PATTERN RECOGNITION RECEPTORS

2) Adaptive immunity: based on antigen-specific responses of T and B lymphocytes

Question 2

The innate immune system is ______ but _________, while the adaptive is ________.

Answer 2

Rapid; non-specific; specific

Question 3

Which arm of the immune system makes the success of vaccines possible?

Answer 3

Adaptive immunity

Question 4

What are the five phases of the adaptive immune response?

Answer 4

1) Antigen recognition
2) Lymphocyte activation (clonal expansion and differentiation)
3) Antigen elimination (antibodies and effector T cells)
4) Contraction (apoptosis of lymphocytes)
5) Memory (some lymphocytes survive in resting conditions)

Native cells expand and differentiate into effector cells in steps 1-3.

Question 5

T cells and B cells are _______ cells of the adaptive immune response. These cells are required for recognition of foreign _______.

Following initial encounter with pathogen/vaccine, ______ T and B cells are established.

Re-exposure to the same pathogen reactivates _____ cells to control the __________ infection quickly and prevent disease.

Answer 5

effector; antigens

memory; memory; secondary

Question 6

(T/F) Vaccines generates the expansion and differentiation of T and B cells like an infection would, creating memory cells.

Answer 6

True!

Question 7

The first encounter with an antigen X produces a ________ response. Antigen X introduced at time zero encounters _____ specific antibody.

After a _____ phase, antibody against the antigen appears; its concentration ____ to a plateau and gradually ______.

When later challenged with antigen X, a very ______ and ______ antibody _______ response occurs, illustrating immunological memory!

Answer 7

Primary; little

Lag; rises; declines

Rapid; intense; secondary

Question 8

Which one of these statements is false?

1) It takes a fairly short time (couple days) to generate memory cells.

2) The more we get exposed to the same antigen, the more rapid and robust the response will be (ex. boosters).

Answer 8

1!

It takes a long time (couple weeks) to generate memory cells.

Question 9

What is the goal of vaccination?

Answer 9

The goal of vaccination is to trigger an immune response MORE RAPIDLY and with LESS HARM than a natural infection: in essence, to avoid the disease that often accompanies the first exposure while enabling establishment of LONG-LASTING IMMUNOLOGICAL MEMORY.

Question 10

A vaccine is a ________ product that can be used to safely ______ an _______ response that confers _______ against infection and/or disease on subsequent exposure to a pathogen.

Answer 10

biological; induce; immune; protection

Question 11

(T/F) Smallpox that caused infections that killed, crippled, or disfigured more than 1 in 20 of all humans is the one of the few human viruses to be eradicated.

Answer 11

False!

Smallpox that caused infections that killed, crippled, or disfigured more than 1 in 20 of all humans is the ONLY ONE human virus to be eradicated.

Question 12

Who is Edward Jenner?

Answer 12

Edward Jenner invented the small pox vaccine.

He noticed all the people that were working with cow milk were developing lesions in their hands. He traced these people and figured out these people never got small pox.

He isolated the virus from the lesion and used it as a vaccine!

Question 13

(T/F) The available smallpox vaccines contain live attenuated vaccinia virus, an orthopoxvirus closely related to variola virus that confers immunity against smallpox virus through cross-reactivity.

Answer 13

True!

Question 14

What is SSPE? What was the consequence of measles vaccine on SSPE?

Answer 14

SSPE stands for subacute sclerosing panencephalitis which is a brain disease that was a late consequence of measles infections in few patients.

When measles was prevented with vaccines, SSPE disappeared 15-20 years later!

Question 15

(T/F) Technical and economic problems can prevent the widespread use of vaccines in developing countries, where mortality from diseases that are virtually eliminated in developed countries are still high.

Answer 15

True!

*there r still many diseases for which we lack effective vaccines

Question 16

Describe herd immunity.

Answer 16

Herd immunity is an important feature of vaccine-induce protection.

If there is no vaccination, infection passes from individuals with disease to susceptible individuals.

If there is vaccination but below threshold for herd population, infection can still pass to susceptible individuals not vaccinated.

If there is herd immunity, infection CANNOT SPREAD in the population and susceptible individuals are indirectly protected by vaccinated individuals.

Question 17

(T/F) Herd immunity is the same for all pathogens (the same % of population has to be vaccinated).

Answer 17

False!

Each pathogen transfers in a different way. Thus, the % of population that has to be vaccinated to protect everyone is different.

Question 18

Why are there still not effective vaccines made for infections like TB, malaria and HIV?

Answer 18

In some infections (malaria, TB, HIV) antibodies are INSUFFICIENT to prevent reinfection or to eliminate the pathogen, and cell-mediated immunity alone is insufficient to provide full immunity.

It is sometimes not the absence of an immune response to the pathogen that is the problem, but rather that this response does not effectively clear the pathogen, eliminate the pathogenesis, or prevent reinfection.

Question 19

(T/F) Measles vaccines are effective worldwide.

Answer 19

False!

They are heat-sensitive, which makes their use difficult in tropical countries; heat stability is being improved!

Question 20

What are the 6 features of effective vaccines?

Answer 20

1) Safety

2) Protective (must protect against illnesses)

3) Gives sustained protection (several years)

4) Induces neutralizing antibody (to prevent infections of cells like neurons that can not be replaced)

5) Induces protective T cells (intracellular pathogens are more effectively dealt with cell mediated responses)

6) Practical considerations: COST, biological stability, ease of administration, few side effects.

Question 21

Which one of the statements is false?

1) Very low toxicity is acceptable in vaccines.

2) Vaccine must be able to generate long-lived memory, important in poorer countries where it is impractical to get boosters.

3) Successful vaccines must induce long-lasting protection while being safe + inexpensive.

Answer 21

1!

Even LOW toxicity is unacceptable in vaccines.

Question 22

Immunization can be passive or active.

Differentiate between passive and active immunization.

Answer 22

Passive immunization: direct administration of the products of the immune response (antibodies/immune cells) obtained from an appropriate donor to a patient. SHORT-TERM effects.

Active immunization: the process of inducing an immune response by exposure to attenuated or killed virus preparations or with purified viral proteins. LONG-TERM effects

Question 23

(T/F) Passive immunization can only be artificially acquired.

Answer 23

False!

It can be NATURALLY or ARTIFICIALLY acquired.

Question 24

Give an example of naturally-acquired passive immunization.

Answer 24

Neonates benefit from passive immunization following birth because some of the mother’s antibodies pass into the fetal bloodstream via the placenta.

This passive process provides transient protection to the immunologically naive newborn.

Question 25

_____ antibodies are secreted in breast milk and transported across the ____ epithelium of newborn where they provide protection against pathogens.

Maternal ___________ is transported across the placenta directly into the ___________ of fetus. Babies at birth already have high levels of plasma _____, with same range of antigen specificity as the mother.

Answer 25

IgA; gut

Immunoglobin G (IgG); bloodstream; IgG

Question 26

At what month does the passive protection (IgG) fall off in a newborn?

Answer 26

It falls at about 6 months as the baby’s own immune response takes over.

Total antibody concentrations are low from 6months-1year after birth.

In this stage, there is an INCREASED SUSCEPTIBILITY to disease.

Question 27

Describe and give an example of artificially acquired passive immunization.

Answer 27

Immunoglobulins from immunized donors or donors recovering from diseases are administered intravenously. The recipient receives immediate short-term protection (weeks/months) but does not develop immunological memory.

Protection against rabies. Preparation of human immunoglobulin is delivered asap to the site of animal contact - this serves to contain virus before it can be disseminated throughout the body.

Question 28

What are the four approaches to produce vaccines?

Answer 28

1) Inactivated “killed” vaccine (no genome)
2) Replication-competent “attenuated” vaccine (do not cause disease)
3) Subunit vaccine (purified components of viruses)
4) Recombinant vaccine (+ mRNA vaccine)

Each use components of the virus the vaccine is targeting!

To date, the most common, commercially successful vaccines comprise attenuated or inactivated particles.

Question 29

How is inactivated “killed” vaccine prepared?

Answer 29

Virulent virus particles are isolated & are inactivated by procedures such as treatment with formaldehyde, UV radiation, or extraction of enveloped viruses with detergents.

Question 30

What are the advantages and disadvantages of inactivated “killed” vaccines?

Answer 30

Advantages: Safe for immunodeficient individuals as the virus can’t reproduce

Disadvantages: Often requires boosters and inactivation methods may have negative effects on antigenicity

Question 31

How can antigenicity of inactivated viruses be improved?

Answer 31

Antigenicity of vaccine preparations can be improved by mixing them with ADJUVANTS.

Adjuvants stimulate immune responses to an antigen. Researches can optimize a vaccine by using DIFFERENT COMBINATIONS OF ADJUVANT and IMMUNOGEN to induce a protective immune response.

Question 32

How do adjuvants work? Give 3 examples.

Answer 32

Adjuvants help localize antigen at the INOCULATION site. They can stimulate the innate immune response (i.e. act as ligands for pattern recognition receptors like TLRs); recruit more immune cells.

Aluminum salt, Emulsions, and Microspheres.

Question 33

Viruses specific for humans may become attenuate by passage in non-human cell lines. What are the four steps of this process?

Answer 33

1) Pathogenic virus is isolated from a patient and grown in human cultured cells

2) The cultured virus is used to infect monkey cells

3) The virus acquires many mutations that allow it to grow well in monkey cells

4) The virus no longer grows well in human cells and may be a candidate for a vaccine

Question 34

(T/F) RNA viruses need to go through more passages than DNA viruses to become attenuated.

Answer 34

False!

DNA viruses need to go through more passages than RNA viruses to become attenuated; RNA viruses have higher rates of mutations.

Question 35

(T/F) Inactivated viruses require boosters while replication competent viruses do not!

Answer 35

True!

Question 36

What are the two ways of constructing an attenuated virus by using recombinant DNA technology?

Answer 36

Clone genome + isolate virulence gene:

1) Mutate virulence gene (some mutations can be reversed back! n virus is not safe)

or

2) Delete virulence gene (safest)

Now, the resulting virus is viable and immunogenic but not virulent! Used as a vaccine!

Question 37

Human papillomavirus vaccine is manufactured using recombinant technology to produce _____ _____ _______.

HPV major capsid protein ___ can fold correctly and self-assemble into empty particles when expressed in _______ cells.

Empty capsids are purified, injected into a person, induces ________ _____ response.

Answer 37

Virus like particles

L1; eukaryotic

Neutralizing antibody

*part of recombinant vaccine

Question 38

How are mRNA vaccines delivered?

Answer 38

They are delivered using NANOPARTICLES!

These protect the mRNA in vesicles so they are not degraded.

Question 39

(T/F) SARS-CoV-2 vaccines are the first mRNA vaccines to be authorized by FDA for emergency use.

Answer 39

True!

Question 40

What are the two essential features that viral candidates for eradication must posses?

Answer 40

1) The virus infectious cycle must take place in a single host
2) Infection (or vaccination) must induce lifelong immunity