Pandemic Flu

Question 1

Name some famous flu pandemics

Answer 1

2009: Swine flu
- 200,000 dead

1918: Spanish flue:
- 50,000,000 dead
- Largest infectious pandemic in history

Question 2

Why is influenza a pulmonary virus?

Answer 2

The virus needs to be activated by proteases. These proteases are found in the respiratory tract.

Question 3

How is the influenza virus built?

Answer 3

RNA segments:

• 8 segments of nucleocapsid protein
• Very prone to mutation

NA: Neuraminidase activity

• Cleaves sialic acid to expose receptors on host cell
• Disrupts mucin barrier

HA: Haemagglutinin activity
- Binds to sialic acid receptors to allow virus entry and release

A strain of virus is named after the structure: HxNx depending on strain of each type.

Question 4

Where in influenza A found?

Answer 4

Ducks

Question 5

What flus tend to infect humans each year?

Answer 5

Influenza A H1: January
Influenza A H1N1: December
Influenza B: March

Question 6

How are influenza vaccines made?

Answer 6

At risk groups (old, asthmatic, pregnant, healthcare workers) receive a vaccine which has purified fraction with HA and NA of an inactivated virus.

Children receive a live attenuated vaccine (primary school children) with a nasal spray.

Question 7

Why can flu have such adverse outcomes?

Answer 7

• High initial dose
• Secondary bacterial infection
• Mutant virus
• Co-morbidity (asthma, obesity, pregnancy)
• Cytokine storm

Question 8

What must flu viruses have to infect humans?

Answer 8

All need a mutation of PB2 627K to enter humans. They also need heightened stability against the environment as they spend longer outside the host. They also need to be able to cut through the mucous layers of the upper respiratory tract.

Question 9

What flu medications are there?

Answer 9

Amantadine

• Targets M2 ion channel
• A single mutation can render this useless
• Almost all influenza viruses are now resistant

Neuraminidase inhibitors:

• Tamiflu (oseltamivir) and Relenza (zanamivir)
• Must be used within 48 hours of infection
• Some resistance is developing

Polymerase inhibitors

• Favipiravin and baloxavir
• Licensed in Japan so far

Question 10

How can a universal influenza vaccine be made?

Answer 10

The head of the vaccine is highly mutating, so a vaccine is impossible. However, studies show a central part of the vaccine is constant, so a vaccine can potentially be made against this.

Difficulty:

• Body mounts immune response to the visible antigens (not the central part)
• Need to somehow make body mount a response to the central part