Larson Influenza Vaccines

How many types of influenza affect humans?

Three types: A, B, C

Type A Influenza

Subtypes determined by hemagglutinin (HA) and neuraminidase (NA)

Type B Influenza

Two lineages:

• B/Yamagata

• B/Victoria

Type C Influenza

Rarely reported as a cause of human illness

Not associated with epidemic disease

How do influenza viruses enter cells?

Attaches and penetrates respiratory epithelial cells in trachea and bronchi

Enters through sialic acid receptors

After influenza enters a cell, replication results in _____

Destruction of host cells

• Regeneration of epithelium takes 3-4 weeks

• Viremia (presence in blood) is rare

Engagement of receptors by influenza leads to _____

• Activation of IRF3, IRF7, and NF-kappaB

• Transcription factors

• Production of IFNs

• Transcription of interferon-stimulated genes

How are CD8 T cells involved in influenza?

Use cytotoxic granules and FasL-mediated apoptosis to eliminate infected cells

How are CD4 T cells involved in influenza?

Trigger B cell activation and promote antibody production to neutralize virus

_____ is important for early recovery from severe influenza

Rapid and prominent CD8 CTL recall

What type of transmission is important for Influenza A virus?

Zoonotic Transmission (Primarily wild aquatic birds)

Reassortment

Swap gene segments to generate a new virus

Which influenza virus is capable of reassortment?

Influenza A virus

Antigenic Shift

Intermixing of RNA from two viruses to make a new virus

Antigenic Drift

Accumulation of mutations over time

Can flu vaccines give you the flu?

No

• IIVs (Inactivated Influenza Vaccines) are inactivated virus, so the virus is “dead”

• Recombinant vaccines include only the Hemagglutinin protein

What does WHO/CDC try to predict about influenza?

Which strains will dominate each year

• Surveillance of people, wild bird populations, farms

• Sample from over 100 different sites worldwide → map movement of the virus

Influenza Vaccine Effectiveness Network

• Measure how the vaccine performs under real-world conditions

• Enroll patients ≥ 6 months old seeking medical care for an acute respiratory infection with cough within 7 days of symptom onset

• Test for influenza and group by vaccine status

Cross-protection in influenza

• Antibodies against one strain of influenza may offer cross-protection against related strains

• One antibody could neutralize multiple strains, at least to some extent (overlapping HA or NA)

Benefit of cross-protection in influenza vaccines

Even if there is a mismatch between the vaccine and circulating strains, the vaccine will often confer some degree of protection