Pandemic Influenza Flashcards
What are the current circulating flu strains
- Influenza A
- H1N1
- H3N2
- Influenza B
- B Yamagata
- B Victoria
H = Haemaglutinin, N = Neuraminidase
Flu (H1N1) in 2018 affecting adults (15-64). In the year before, H1N1 didn’t really affect this age group. Why might this be?
Original Antigenic Sin
Explain the concept of Original Antigenic Sin
The immune system encounters virus with dominant antigen X.
It induces a strong immune response to this virus through X-specific antibodies.
As time goes on, virus evolves and X may become the recessive antigen, and Y the dominant
Immune system still recognises the recessive X and so memory produces antibodies against the recessive instead of the dominant Y.
The response is weaker and therefore, body is susceptible
Which flu strain is currently affecting the elderly?
H3N2
Which influenza category can not causae pandemics? Why is this?
Influenza B
Flu B is ?contained in human hosts (i.e. human reservoir), so their antigenic drift is not too different each time
Flu A has animal reservoirs so there are antigenic shifts - everyone will be naive to them
What is the difference between antigenic drift and shift
Antigenic drift: Natural mutation/variation of antigens in viruses leading to subtle differences in surface proteins
Antigenic shift: New virus emerges from two viruses - new virus has mixture of both anigens - flu A as there is animal and human reservoir
Which flu strain caused the pandemic in 2009
H1N1 (Swine Flu)
The first case of H1N1 was in April and the first peak was in the Summer. There was a second increase in Sep which led to a second wave in winter 09/10. Why was there an increase
September is when children went back to school
There was a 3rd wave of the H1N1 flu from Dec 2010 to Feb 2011. Who did it affect the most and why could this be?
- Virus had just come from animal reservoir in 2009
- The first two waves allowed for selection of virus which had better survival and increased immunogenicity
- Third wave could be due to the highly immunogenic and reactogenic strain
Which three new risk groups were identified in the 2009 pandemic
- Obese
- Pregnant
- Immunocompromised
Through Genetic Analysis, what genetic polymorphism was identified to be associated with influenza suscepitiblity
IFITM3
Interferon Stimulated Gene, CC (?recessive) impaired IFITM3 function
The flu pandemic in 2009 also showed that cellular immunity protectsagainst flu illness. How?
CD8+ cells againts the flu were able to control viral load and therefore lead to fewer symptoms
New approach to vaccine? Allow infection but viral load low enough not to cause illness
Influenza morphology: Influenza is a _____-sense single-stranded RNA virus. It has _____ RNA segments. On the surface it has Haemaglutinin and _____ along with _____ ion channel. It also has a RNA _____ that it needs to replicate once in the host cell.
Influenza morphology: Influenza is a negative-sense single-stranded RNA virus. It has 8 RNA segments. On the surface it has Haemaglutinin and neuraminidase along with M2** ion channel. It also has a RNA **polymerase that it needs to replicate once in the host cell.
Outline the cell cycle of the influenza virus.
- Bind target cell
- Endocytosis
- Release 8 RNA segments
- mRNA synthesis (surface proteins)
- RNA replication
- Protein synthesis and RNP formation
- Assembly
- Release by neuraminidase action
RNP = Ribonucleoprotein particle
What two licensed drugs do we have and what are their MOA
- Adamantanes - M2 ion channels
- Amantidine
- Neuraminidases - inhibits neuraminidase
- Tamiflu
- Relenza
Overall, relenza has better efficacy and less SE than tamiflu. despite this, tamiflu is preferred - why is this?
- Tamiflu taken orally whilst relenza is nasal inhalation
- Easier to stockpile oral tablets in preperation for pandemics
Describe how anti-virals become ineffective.
Natural selection and shift through selection pressuress
- Using anti-viral A selects for virus with resistance to it
- Resistant virus propagates
- Anti-viral B use decreases viral load, but again selects for resistant strains
- Cycle
Describe the development of a flu vaccine
- Epidemic virus doesn’tgrow well in egg
- Innoculated with virus that can grow in egg
- RNA segment reassortment to give a virus that is able to grow well in eggs but have the surface proteins of the epidemic flu
What are some influenza vaccine types used today in the UK
- Inactivated
- Split or subunit HA
- Live attenuated
Pandemrix is a novel adjuvant used but caused narcolepsy. Explain how this happened
- Antibodies against H1N1 nuceloprotein has cross-reactivity with hypocretin in the hypothalamus
- Antibodies can cross the blood brain barrier
- Antibodies disrupt signalling by
- Direct blockade
- Secondary depletion of hypocretin fomration
