Influenza Virus and Vaccine

Question 1

What does influenza A infect?

Answer 1

• humans, swine, and avians (equines, marine mammals, bats, dos)
• capable of antigenic drift and shift
• cause of most epidemics and all pandemics

Question 2

What does influenza B infect?

Answer 2

• humans and seals
• capable of genetic drift
• rare epidemic and no pandemic

Question 3

What is the cause of influenza being able to reinfect people and the reason the flu vaccine is changed?

Answer 3

• antigenic drift: small changes in virus (mutation)
• specific mutation: in hemagglutinin envelope protein which allows the virus to escape neutralizing antibodies

Question 4

What type of virus is influenza?

Answer 4

• orthomyxovirus
• negative sense
• segmented RNA (8 segments)
• helical
• enveloped

Question 5

How is influenza spread?

Answer 5

• person to person via respiratory droplets and fomites

Question 6

How is influenza killed?

Answer 6

detergents, heat, acid, or drying due to enveloped virus

Question 7

Why should you NEVER give aspirin for influenza or chickenpox?

Answer 7

• lead to Reye syndrome due to salicylate causing mitochondrial dysfunction

Question 8

Do people die with influenza?

Answer 8

Yes… most deaths are people older than 65

• people who are hospitalized are usually due to underlying health conditions and children

Question 9

What is the difference in children and adults in the pathogenesis of influenza?

Answer 9

• adults shed virus one day before symptoms to 5-7 days after
• children shed up to 10 days after symptoms

Question 10

How does pneumonia occur usually from influenza?

Answer 10

• usually secondary bacterial pneumonia
• if primary viral pneumonia from influenza, high fatality rate

Question 11

How can even the healthy get a secondary bacterial pneumonia infection?

Answer 11

• killing airway epithelial cells make it easier for bacteria to bind in airway
• influenza can kill alveolar macrophages that help prevent bacterial infection
• airway edema and dead cells create nutrient rich environment for bacterial growth
• viral neuraminidase inactivates some innate antimicrobials that might help kill bacteria and expose bacterial attachment sites

Question 12

Why does the flu change from year to year?

Answer 12

• antigenic drift in hemagglutinin

Question 13

In the pathogenesis of influenza, what does the viral hemagglutinin bind to?

Answer 13

silica acid: a2-6 linkage
- present in the upper respiratory tract at high levels and only in lower respiratory tract at low levels

Question 14

What are the types of flu vaccines?

Answer 14

• inactivated influenza vaccine: detergent disrupted inactivated virus with HA and NA put in the vaccine
• live attenuated influenza vaccine: cold adapted influenza virus containing HA and NA in the inactivated vaccine
• subunit vaccine: entirely recombinant HA protein grown in cell culture
  all are quadrivalent meaning they contain 2 strains of influenza A and 2 strains of influenza B

Question 15

How is the vaccine for influenza picked up?

Answer 15

• vaccine is picked up before the flu season where strains of influenza are prevalent in other parts of the world

Question 16

How long does it take to be protected after vaccination?

Answer 16

• 2 weeks

Question 17

What are the neuraminidase inhibitors and what are the MOA?

Answer 17

• Zanamivir and Oseltamivir: Tamiflu
• MOA: prevent budding and release of virus so must be used within 2-3 days of infection to have maximal effect
• has side effects of nausea and vomitting

Question 18

How does Baloxzvir/Xofluza work?

Answer 18

• cap-dependent endonuclease inhibitor
• MOA: blocks ability of virus to snatch caps so can’t transcribe viral mRNA
• also must be used within 48 hours

Question 19

How many people were infected in the 1918 flu epidemic?

Answer 19

• 1/3 to 1/2 of world’s population
• fatality rate of over 2.5%
• W shaped mortality curve: more deaths in 18-40 age range than normal

Question 20

What’s the difference between avian strain and the human strain?

Answer 20

Avian strain:
- recognizes a2,3 sialic acid linkage
- present in more of lower respiratory tract
- so more severe infection, but less spread

Human strain:
- recognizes a2,6 sialic acid linkage
- present in more of upper respiratory tract
- so not as severe because not much in lower tract, but easily spread

Question 21

What made the 1918 strain so fatal… what’s the difference between that and the seasonal one now?

Answer 21

• had the PB1-F2 virulence factor
• it could infect both upper and lower respiratory tracts, so severe and efficient person-to-person spread
• replicated more efficiently, cause apoptosis CD8 and alveolar macrophages which increases inflammatory response and increases cellular infiltrates of lung airways (cytokine storm)
• almost all recorded deaths showed bacterial confection (93%)
• little prior immunity in population

Question 22

How is bird flu spread?

Answer 22

• birds excrete influenza in droppings
• most infections occur from contact with birds (domestic poultry)
• not usually person-to-person spread

Question 23

What is HPA1/LPA1?

Answer 23

• high pathogenic or low pathogenic avian influenza
• based on ability of virus to kill chickens; not humans

Question 24

What are the 2 main avian influenzas in bird flue that has crossed over to infect humans in substantial numbers?

Answer 24

• H5N1: 31-53% fatality; HPAI influenza; can cause devastation in poultry industry
• H7N9: 45% fatality; LPAI and HPAI influenzas

Question 25

What has China been doing in regards to vaccines for bird flu?

Answer 25

vaccinating poultry with an H5/H7 vaccine