1. Describe the potential for changes in herpes zoster incidence related to varicella vaccination of children, and how, if at all, these have impacted vaccinated populations.

According to the predicted impact after varicella vaccination of children on Herpes Zoster from mathematical models, zoster cases are expected to increase until 20 years of vaccination. After that, zoster cases would decrease gradually and reach the same number of cases after 40 years of vaccination. Thereafter, the incidence rate is expected to decrease significantly and become a rare disease decades later. Currently, it is recommended for all adults US-born after 1980 who do not have evidence of immunity to varicella to receive 2 doses of varicella vaccine. Decades later, if all adults have evidence of immunity to varicella after vaccination in childhood, varicella vaccination recommendations would only need 1st dose at 12-15 months and 2nd dose at 4-6 years.

What is a therapeutic vaccine?  How might this principle be useful for HIV control/prevention? (3pts) 

A therapeutic vaccine is one in which is used after infection occurs, aiming to induce immunity to alter the course of disease. Although vaccines are mostly prophylactic but in the recent years there have been significant developments towards therapeutic vaccines for infectious diseases like AIDS and Tuberculosis, gastric ulcers, cancers and autoimmune diseases.

Research is ongoing to develop a therapeutic HIV vaccine that is designed to improve body’s immune response to HIV in a HIV positive person by ramping up immune system to find and kill HIV infected cells and by preventing or limiting HIV for making its copies. In this way, these vaccines would not only slow down progression of HIV to AIDS but also decrease viral load to a level that it makes less likely for patient to transmit HIV to others, thereby playing its part in control as well as prevention of disease.

Why do serogroup B meningococcal vaccines present unique challenges for development?  What makes them different from other available meningococcal vaccines?

Serogroup B Meningococcal vaccines present unique challenge for development because strategy used for other meningococcal vaccines (serogroups A, C, W, and Y) does not work for it. Vaccines for other serogroups induce an immune response against the polysaccharide capsule around the bacterium. However, the capsule polysaccharide of group B meningococcal bacteria is structurally similar to certain abundant human glycoproteins like NCAM. It is therefore not a suitable target due to risk of autoimmune damage through a mechanism called immune mimicry. The unique challenge to development of serogroup B meningococcal vaccine has two facets: the difficulty in developing a vaccine in general and specific challenge of creating a vaccine against a pathogen that mimics host molecules.

Why do we see measles outbreaks in the post elimination era in the United States?

In 2000, the United States declared measles was eliminated (absence of continuous disease transmission for greater than 12 months) within the United States. However, we still see measles outbreaks in the United States because of measles outbreaks in some other countries came into the United States by international travelers and there were spreads of measles infection by unvaccinated people within United States communities.

• In the context of the pneumococcus vaccine (Streptococcus pneumoniae), what is serotype replacement? (3 points)

Serotype replacement is an untoward effect of the widespread use of pneumococcal conjugate vaccines that has led to emergence of nonvaccine pneumococcal serotypes, termed as replacement strains. These vaccine related and non-vaccine serotypes include 6C, 19A, 15A, 15B etc. These new serotypes       appear as colonizers of the nasopharynx and as a cause of pneumococcal disease both in vaccine recipients and in general population at large. Reduction in nasal carriage of PCV serotypes appears to create an ecological niche for non-vaccine serotypes. For example, Streptococcus pneumoniae type 19 emerged as a most common cause of pneumococcal disease in children and adults a few years after universal vaccination with PCV7 in USA. The very strain was then added to the PCV13. However, since introduction of PCV13, other emerging serotypes not contained in vaccine emerged. Examples include 15B, 23B etc.

• How do the immune responses produced by PCVs and PPSVs differ? (3 pts)

Pneumococcal Conjugate Vaccine (PCV)

1. PCV produces more robust immune response by using both T and B cells
2. It results in mucosal immunity.
3. More than 90% effective against invasive disease caused by vaccine serotypes in children.
4. 45% effective against vaccine-type non-bacteremic pneumococcal pneumonia in adults > 65 years of age

Whereas,

Pneumococcal Purified Polysaccharide Vaccine (PPSV)

1. Pneumococcal purified polysaccharide vaccine produces its response by stimulation of B cells which release IgM without assistance from T cells.
2. Not effective in children younger than 2 years.
3. 60%–70% efficacy against invasive disease.
4. Less effective in preventing pneumococcal pneumonia

• In the context of influenza, what is the “original antigenic sin”? What implications does this have on control?

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