Challenges of Vaccine design

Question 1

Which of the following is NOT a characteristic of passive immunity?

Passive immunity is normally short-lived

Passive immunity results when a person is given someone else’s antibodies

Passive immunity can protect by stimulating production of pathogen-specific antibodies by the recipient that then activate ADCC and complement to clear the pathogen

Passive immunity can lead to ‘serum sickness’

Passive immunity results in immediate protection

Answer 1

Passive immunity can protect by stimulating production of pathogen-specific antibodies by the recipient that then activate ADCC and complement to clear the pathogen

Passive immunity results from when a person is given antibodies from an external source. This could be natural- mother’s antibodies transferred to infant or artificial where antibodies are derives either from immune people or non-human immune animals (e.g horses , sheep , rabbits). It is quick acting and can produce a response within hours to days. However, sometimes severe allergic reaction to the administered antibody (animal source) can cause serum sickness. Moreover the immunity conferred here is short-lived because long-lasting immune cells are not generated.

Question 2

One of your classmates is bitten by a poisonous spider, whose venom causes paralysis within two to three days. Life-saving treatment would BEST consist of which of the following?

(A) Immunisation with venom toxoid protein. This will induce an antigen-specific neutralising humoral immune response

(B) Transfer of venom-specific T cells

(C) Transfer of immune serum derived from a horse that had previously been immunised with spider venom

(D) Transfer of activated B cells that secret venom neutralising antibodies

(E) Immediate immunisation with a viral vaccination vector expressing the venom toxoid. This will induce a protective, antigen-specific T cell-mediated response

Answer 2

Transfer of immune serum derived from a horse that had previously been immunised with spider venom

Due to the fast-acting venom, a quick response is required to counteract the toxic effect of the spider venom. The speed of the immune response generated by the above strategies are (fastest to slowest): c > d > b > a > e

Question 3

Which of the following three refers to a vaccine derived by deleting the pathogenic genes from a pathogen?

Attenuated
Killed
Subunit

Answer 3

Attenuated

Question 4

Of the following three vaccine formulations, which one is the most effective?

Attenuated
Killed
Subunit

Answer 4

Attenuated

Live attenuated: these vaccines often consist of a pathogenic strain in which the virulent genes are deleted or modified. Thus, they contain a version of the living microbe that has been weakened in the laboratory so it can’t cause disease. A common way to attenuate the pathogen (usually virus) is through serial passage in hostile environments, i.e. cells in which they do not reproduce very well. As the pathogens evolves to adapt to the new environment, they become weaker with respect to their natural host. This is the method that has been used to produce the measles and mumps vaccines. Attenuation can also be achieved by irradiation (a dose high enough to attenuate but too low to kill the pathogen) although this is still only in experimental vaccines, e.g. irradiated cercariae for schistosome vaccine and irradiated sporozoites for malaria vaccines. These vaccines induce long lasting immunity but can be fragile requiring cold storage and carry the risk of mutation to pathogenicity. Examples of these vaccines include the virus vaccines oral polio, measles, mumps, rubella, yellow fever and the bacteria vaccines BCG and cholera.

Inactivated or killed vaccines: In these vaccines, the pathogen is grown in animals (vaccinia in calves for smallpox; rabbit brains for rabies), bacterial culture (Cholera vibrio) or eggs (influenza, vaccinia) and then inactivated using various approaches such as chemicals, heat, or radiation. Unlike the live attenuated vaccines, inactivated vaccines are not live and do not exhibit a molecular change. They induce intermediate levels of immunity and several doses (booster vaccination) may be required. Examples of these vaccines include the virus vaccines Hep A, Salk polio and the bacteria vaccines pertussis and cholera.

Sub-unit vaccines: Do not use entire virus or bacteria (pathogenic agent). These vaccines are made using components of pathogenic organism not whole organism e.g. Hep B. Subunit vaccines can contain anywhere from 1 to 20 or more antigens .The subunits are produced through recombinant protein expression e.g. in E.coli. Examples of these include the toxoid vaccines (e.g. tetanus, Hep B, occellular) conjugate polysaccharide vaccines linked with suitable carrier proteins (e.g. meningitis and pneumonia) as well as single and polyvalent vaccines

Question 5

What are adjuvants used for?

Question 6

What role do DCs play in vaccination?

Question 7

Give broad outline of the steps needed for vaccine approval

Question 8

What are the different types of vaccines and what are their purposes?

Question 9

How many phases are there in vaccine trials and what are they for?