Week 5 - Vaccines to Prevent Respiratory Infections

Question 1

Why promote vaccines for respiratory infection if protection is not complete?

Answer 1

Populations can benefit from prevention of severe disease outcomes (“Wild to Mild”)

Question 2

What is critical to understanding vaccine performance?

Answer 2

Surveillance

Question 3

What are some advances in vaccine scientific research?

Answer 3

• Protein conjugate vaccines reduce carriage of Strep. pneumoniae
• Understanding etiology of severe, progressive seizure disorder following DTP vaccine
• Supports importance of conformation of the RSV F protein to eliciting an effective immune response

Question 4

What is a vaccine?

Answer 4

Vaccines are a biological product that elicit a specific immune response to specific disease-causing agents - use the body’s own immune response to provide protection

Question 5

How do vaccines provide direct and indirect protection?

Answer 5

Direct: immunity for vaccinated persons

Indirect: limit circulation of infectious agents and exposure of susceptible persons

Question 6

Provide examples of challenges for preventing respiratory infection by vaccination

Answer 6

• The respiratory tract is a common portal of entry for infectious pathogens -> injected vaccines may not provide enough protection at point of entry (but can still prevent severe outcomes)
• Respiratory compartment has its own subdivision of immune system and tools (mucosal immunity) to fight off pathogens

Question 7

What is herd immunity?

Answer 7

When a sufficient proportion of a population is immune to an infectious disease (through vaccination or prior illness) to make its spread from person to person unlikely. Even individuals not vaccines (such as newborns or those with chronic illness) are offered some protection because the infection has little opportunity to spread within the community

Question 8

What is active immunization?

Answer 8

Administration of specific components of an infectious agent to elicit immune response in recipient

• Immunology memory provides prolonged protection
• Traditional vaccines provide active immunization for recipient

Question 9

What is passive immunization?

Answer 9

Transfer for preformed antibody produced externally to provide protection to the recipient

• Provides temporary protection that wanes with time
• Transfer of maternal antibody across the placenta that provides protection in early infancy is an example of passive immunization

Question 10

What is influenza?

Answer 10

A viral infection that causes febrile respiratory disease

• Seasonal outbreaks associated with circulation associated with circulation of multiple influenza viruses

Question 11

Define “drift” and “shift”?

Answer 11

Drift: Viruses continually evolve in small ways

Shift: Emergence of new viruses

Question 12

How does influenza vaccine strain selection work?

Answer 12

Influenza composition is reviewed each year and updated as needed, based on best available information and recommendation of experts

• WHO experts convene in September (Southern Hemisphere) and February (Northern Hemisphere) > National regulatory authorities determine strain selection after WHO recommendations made

Question 13

What are key challenges in strain selection?

Answer 13

1. Vaccine effectiveness depends on match between hemagglutinin (HA) of vaccine and HA of circulating strains of virus
2. Timelines for influenza vaccine production are relatively fixed
3. Availability of reference strains (candidate vaccine viruses) suitable for vaccine manufacture

Question 14

What is the timeline for egg-based seasonal influenza vaccines?

Answer 14

Jan-Mar: virus selection
Apr-Jun: FDA testing, licensure
Jul-Sep: filling/packaging
Sep-Oct: product release/shipping
Oct-Jan: vaccination

Question 15

What do we know about Influenza B/Yamagata Lineage Viruses?

Answer 15

• No confirmed detections circulating after March 2020
• We can’t be confident that it’s extinct
• GISRS will continue to actively conduct targeted surveillance for Yamagata

Question 16

What is Pneumococcal Disease?

Answer 16

Caused by infection with bacteria streptococcus pneumoniae

• Non-invasive local infection (pneumonia, otitis media) or invasive disease (bacteremia, meningitis)
• Polysaccharide vaccines and protein conjugate vaccines

Question 17

What is Pertussis (Whooping Cough)?

Answer 17

Highly contagious respiratory disease
- severe, debilitating could illness, can impact all ages
- “100 day cough”
- vaccine preventable

*Poorly controlled despite high vaccine coverage

Question 18

Why is Pertussis poorly controlled despite high vaccine coverage?

Answer 18

Original whole-cell vaccine worked well, but very reactive (fever, swelling, fussiness)

Because of concern, switched to acellular (DTap) -> many limitations, but can be given during pregnancy because it is less reactive (great passive immunization strategy) -> Did not provide sustained protection -> shift to adolescent/adult formulation (TDap)

Question 19

How is the DTP vaccine and Dravet Syndrome connected? (think: case study)

Answer 19

DTP vaccine caused fevers, which elicited seizures related to Dravet Syndrome (hence why more seizures escalated at the time of DTP vaccine rollout)

DTP did not cause Dravet Syndrome - it was in the individual regardless of the vaccine

Question 20

What is Respiratory Syncytial Virus (RSV)?

Answer 20

• Leading cause of hospitalization in US infants
• Causes fair amount of illness in extremes of life (v young or v old)
• Discovered in runny noses of chimpanzees

Question 21

Why were early clinical trials for RSV a nightmare?

Answer 21

Formulin-inactivated RSV vaccine hospitalized 80% of children who received vaccine (in clinical trial) because it developed poor functional antibody response (Th2-biased CD4 T cell) causing more severe outcomes when individual became infected

Question 22

What are some scientific advances that led to new approaches to RSV prevention?

Answer 22

1. RSV protein mediates fusion of virus with host cell membrane at 2 major conformational states: pre-fusion and post-fusion
2. In 2013, discovered structure of pre-fusion that is highly protective
3. When stabilized, pre-fusion F protect produced excellent protective antibody response

(something something pre-fusion is the “but crack of the back” vs. post-fusion “standing up”??)