Immunity to Influenza Flashcards
What is influenza?
Influenza is a disease caused by the dsRNA influenza viruses
A, B, and C subtypes, although C is theorised to have been eliminated during the COVID pandemic
What is IAV?
Influenza A Virus
Causes the largest burden of the influenza subtypes
Is able to infect a wide variety of hosts, as its haemagglutinin protein (HA) binds sialic acid, present on different cells in different species
What specific sialic acid bonds do different IAV strains bind to?
Avian IAV strains preferentially bind to α2,3-linked sialic acid, which is common in birds’ intestinal tracts.
Human-adapted IAV strains bind to α2,6-linked sialic acid, abundant in the human upper respiratory tract.
How do different human IAV strains vary?
infect large number of ppl, however the young, old, and immunocompromised experiencing the worst burden
some strains (eg Spanish Flu) disproportionally affect the young, some more transmissible, some more deadly
eg
H1N1 viruses - more lethal
H3N1 viruses - less lethal but more pathogenic and transmissible (pandemic potential)
nomenclature = Specifies the hemagglutinin (H or HA) and neuraminidase (N or NA) protein subtypes
How are influenza vaccines typically produced?
– Selected strains (which are predicted to be prevalent in the winter) which are adapted to grow in chicken eggs
– fertilised eggs are inoculated with virus and incubated
– viruses are collected from allantoic fluid and chemically inactivated
– antigens are purified
the process from strain selection to vaccine availability takes around 6-8 months
What are Cell Culture-Based Influenza Vaccines and how are they an improvement over egg based vaccines?
Commonly uses mammalian cell lines such as African green monkey kidney (Vero) cells
The selected virus is introduced into the cell cultures instead of eggs
Virus replication occurs in bioreactors with controlled conditions
Similar steps for virus inactivation, purification, and formulation follow
Faster Production: Cells can be grown and scaled up more quickly than fertilized eggs
Fewer Mutations: Reduces the risk of adaptive mutations that occur in eggs, potentially improving vaccine match and efficacy
No Egg Dependency: Bypasses reliance on egg supply chains and avoids issues with egg allergies
Scalability: More easily scaled up to meet pandemic demands
egg based is still the vast majority, but cell based is growing with one vaccine (Flucelvax) approved for use in the US
What is a downside to antiviral influenza medications?
most anti-viral drugs target the replication of the virus
neuraminidase inhibitors prevent release from a cell, so virus sits on outside of cell making it accessible to immune system
only used as a preventative in old people as they are only effective at beginning of infection but symptoms only arise a few days in
Explain the NP+M1 combination vaccine?
NP: influenza nuclear protein. Plays critical role in replication and transcription of viral genome
M1: involved in assembly and budding of new virus particles
both highly conserved
The vaccine can be designed using recombinant protein or viral vector platforms, which are scalable and do not require adaptation to specific strains each year
These proteins are degraded in the cell and presented on MHC class I, inducing a T cell mediated response
currently in phase II clinical trial - evaluate safety and efficacy of vaccine
What are chimeric hemagglutinins and how are they being used in vaccine development?
cHAs
combines conserved stalk domain from a human strain and a novel head domain from a non-human strain
– novel head is to minimise immune system’s response to it and to focus on stalk
The stalk domain of HA is essential for viral entry and is much more conserved across influenza subtypes than the highly variable head domain
cHA vaccines reduce reliance on accurate predictions of circulating strains, as they provide heterosubtypic immunity
antibodies against stalk are found to be v powerful (neutralising Abs, prevent viral entry)
however vaccination may just influence high rates of stalk mutation, however I believe that doesn’t not mean we shouldn’t try
What is influenza M2 and how effective would a vaccine against it be?
M2 is an ion channel protein on membrane which activates in acidic environment from endosome which allows entry of protons, and subsequent uncoating and release of viral ribonucleoproteins
anti-M2 antibodies are not neutralising but can generate Fc receptor mediated processes such as opsonisation and neutrophil recruitment
What is meant by “influenza is a disease of damage”?
images show destruction of lung epithelial cells, and a significant decrease in space for gas exchange, which is why it is lethal in young, old, and immunocompromised individuals
but after infection has resolved, it is hown that repair is extensive and evidence that this is driven by lung progenitors (basal & AT-II)
