Genetics - Lecture 25: COVID 19 Vaccines

Coronavirus

named after their appearance which looks like a sun

Genome of a coronavirus

single stranded positive sense RNA

Zoonotic coronavirus

jump from animals to humans; all beta-coronaviruses

ORF1ab

large part of SARS=CoV-2 genome that codes for a mega-protein that is then cleaved into 16 non-structural proteins

ACE2

Human COVID-19 receptor protein

TMPRSS2 protease

Efficient viral entry requires cleavage of spike by this protease

Lateral flow immunoassays

-Labeled antibody reacts with the antigen as the sample moves through the pads and membranes of the test strip

-As the mixture migrates, antigen-antibody complexes are captures at a test line by immobilized antibody

Non-neutralizing antibodies

clump-up virus particles - large clumps more easily cleared by phagocytes

Neutralizing antibodies

block pathogen function directly

Traditional vaccines

weak or dead pathogens

Immunogenicity

Ability of pathogens to induce an immune response

Major challenge with traditional vaccines

need to grow lots of virus and kill it or inactivate it without loosing immunogenicity and without harming people

3 Modern strategies for making vaccines

1. Protein-based

2. Viral vector

3. mRNA

Main vaccine antigen

spike protein

Protein vaccines

recombinant proteins from virus injected to elicit immune response

Problem with protein vaccines

proteins do not invade cells, so may not get a strong T-cell response

Viral vector vaccines

Put SARS-CoV-2 spike protein gene into crippled adenovirus genome

mRNA vaccines

mRNA from virus placed into lipid nanoparticle which delievers the mRNA to body cells

Benefits of mRNA vaccine

Faster and potentially safer than viruses to make: RNA and shell are completely synthetic

Two challenges of mRNA vaccines

- creating a lipid nanoparticle than can survive to fuse with a cell

- mRNA degredation in cells

Method to prevent premature degredation of mRNA from vaccines

Modified urasil bases that translate correctly, but are resistant to degredation

Spike protein with S-2P mutation

locked into pre-fusion conformation

Vaccine with S-2P:

elicit anibodies to close spike protein (pre-fusion conformation) to prevent binding to ACE2, thus neutralizing virus

Vaccine-escape spike protein variants:

- reduce binding to neutralizing antibody

- maintain binding to ACE2 receptor

Difference between Omicron and the previous variants

Omicron spike did not require TMPRSS2 cleavage for efficient entry

Why did variants before omicron infect deep into the lungs?

TMPRSS2+ cells are found deep in lungs

Where did omicron primarily infect?

upper resperatory tract, because those cells do not have TMPRSS2

Why was omicron more virulent, but less deadly?

more virus in the upper respiratory tract, thus easier to cough out and spread, BUT, not found deep in lungs and therefore less pneumonia