Sars CoV-2 Study guide
Critical and Deceased w/COVID
- ARDS -Acute Cardiac Injury -Multi-organ failure
Genetically Engineered Viruses
- Adeno virus vaccine and adenovirus is modified to make the SARS-CoV2 spike protein - The adenovirus infects your cells (once) and cannot replicate - Your cells make and present the spike proteins
Inactivated Virus
- Culture SARS-CoV2 in the lab, inactivate the virus with heat or chemical treatment -Sinopharm, Sinovac, Bharat Biotech
Severe Disease w/COVID
- Dyspnea -Coexisting Illness -ICU needed
Cons of adenovirus vaccines
- Efficacy appears to be lower than mRNA vaccines - Immunity to adenovirus may limit effectiveness of booster shots and/or subsequent use of the Ad vector in other vaccines (the two Ad vector approach of Gamaleya may get around this an may be why they have higher claimed efficacy)
Cons of the Subunit Protein Vaccine
- Efficacy appears to be lower than the mRNA vaccines - Will not yet generate a strong Tc response -Not yet approved but submitting for approval by the end of 2021
SARS-CoV-2 Attachment and Entry
- Enters cells through ACE2 receptor (found in airways, heart, lungs, kidneys and GI tract, others) -Entry begins with attachment of S glycoprotein to ACE2 -Process of S glycoprotein by TMPRSS2 is necessary for fusion -Followed by fusion of viral membrane and host cell, conformational changes in S and ACE2, and entry -Certain nasal epithelial cells have the highest ACE2 expression in the respiratory tract
Pros of Adenovirus Vaccines
- Fairly affective (about 80% on average) - Relatively easy to produce (adenoviruses are easy to culture) - Fairly easily modified to be effective against variants - Since the spike protein is made internal to your human cells, it mimics a natural infection and thus good B, Th and Tc cell responses are produced - Less stringent storage and shipping requirements than mRNA vaccines (refrigerated for a few months)
Mild Disease w/COVID
- Fever, fatigue, and dry cough - Ground-glass opacities - Pneumonia
Pros of the MRNA Vaccines
- Highly effective in 95% of clinical trials -Relatively easy to produce (not limited by culture) -Easily modified to be effective against variants -Since the spike protein is made internal to your human cells, it mimics a natural infection and thus good B, Th and Tc cell responses are produced
Protein Subunit Vaccines
- Provide the SARS-CoV2 spike protein directly -Novavax
Pros of Inactivated Virus Vaccines
- Relatively Inexpensive to produce -Less stringent storage and shipping requirements than mRNA vaccines (refrigerated for a few months)
Pros of the Subunit Protein Vaccine
- Relatively inexpensive to produce - Less stringent storage and shipping requirements than mRNA vaccines (refrigerated for a few months) -Efficacy appears to be higher than a adenovirus and inactivated vaccines (89%) -Generates a very strong antibody response (4-8x above natural infection)
Corona Virus induced Disease
- SARS-CoV2 is the virus - COVID is the disease that it carries
Examples of Inactivated Virus Vaccines
- Sinopharm -> Selected a virus that grows well in vero cell culture -> Inactivated with beta-propiolactonem Al adjuvant -> 79% effective, approved in about 70 countries - Sinovac -> Similar approach to Sinopharm -> Efficacy just over 50%, limited use in China and trials in Brazil - Bharat Biotech (Covaxin) -> Similar approach to Sinopharm -> 77.8% effective against preventing symptomatic infection, 93.4% against severe disease, authorized for emergency use in India
Benefits of wearing a Mask
- They filter respiratory droplets FROM the WEARER - They reduce the velocity of droplets from the wearer -They also provide some filtering of incoming particles to the wearer
Inactivated Virus Vaccines
- Viruses that were previously isolated from human patients and are grown in tissue culture (Vero cells-kidney epithelial cells from an African green monkey) -Virus is isolated and chemically inactivated and mixed with adjuvant to make the vaccine
Genetically Engineered Viruses
- expresses the SARS-CoV2 spike protein, generally the virus is easily cleared -Johnson and Johnson (Janssen vaccine), Oxford AstraZeneca, Gamaleya
How do MRNA Vaccines Work?
- mRNA coding for spike proteins is encapsulated in lipid nanoparticles. Fusion delivers mRNA to cytosol -Your cells make SARS-COV2 spike protein and display it on the membrane (similar to a natural infection) -B cells that recognize displayed proteins develop antibodies -Cells also process the spike protein and present it on surface via MHC class 1 (similar to a natural infection) -Vaccinated cells that die release spike proteins that can be taken up by dendritic cells and phagocytes for presentation on MHC class 2 - Good Th, Tc and B-cell responses are generated
Cons of Inactivated Virus vaccines
-Efficacy appears to be lower than the other vaccines -Lacking somewhat in published clinical trial data - Will not generate a strong Tc response - Inactivation must be carefully done (risk of infection if virus is not inactivated) -Difficult to rapidly switch to new strains as a virus mutates
Subunit Protein Vaccines
-Novavax - The SARS-CoV2 protein is cloned in a baculoviral, which is used to infect moth cells in culture -Spike proteins are assembled into nanoparticles and injected into adjuvant
mRNA Vaccines
-Provide mRNA that codes for SARS-CoV2 spike protein, your cells make the protein -Pfizer/BioNT and Moderna
Cons of mRNA vaccines
-Relatively stringent shipping and storage requirements - Expensive -Requires 2 doses for best protection -Rare allergic reactions to the shot
Receptor SARS-CoV2 uses
ACE2 Receptor
Inactivated Vaccine Risk of Mutation to Virulence
Absent
Inactivated Vaccine Risk to immunocompromised Patient
Absent
ARDS
Acute Respiratory Distress Syndrome
Proposed Routes of SARS-CoV-2 Transmission
Aerosols, Airborne, Contact/Droplet
Type of virus SARS CoV-2 is
An enveloped non-segmented positive sense RNA virus
Immunologic Adjuvant
An ingredient of a vaccine that may promote a better immune response
Attenuated vaccines/Inactivated Vaccines with COVID
Attenuated Vaccines not available for SARS-CoV2, inactivated vaccines available but difficult to produce in large quantity
Attenuated Vaccine Types
Attenuated Viruses, attenuated bacteria
Attenuated Vaccine Risk to immunocompromised recipient
Can be Significant
Zoonotic diseases
Diseases caused by germs that spread between animals and people
Pneumonia
Fluid within the lungs
Attenuated Vaccine Cell-mediated immune response
Good
Inactivated Vaccine Stability in warm temperature
Good
Reservoir
Habitat in which an infectious agent normally lives, grows and multiplies
Inactivated Vaccine Antibody Response (Memory)
IgG
Attenuated Vaccine Antibody Response (memory)
IgG; secretory IgA if administered orally or Nasally
Inactivated Vaccine Types
Inactivated whole agents, toxoids, subunit vaccines, VLPs, polysaccharide vaccines
Asymptomatic Period
Incubation period for COVID
Inactivated Vaccine Route of administration
Injection
Attenuated Vaccine route of administration
Injection, oral or nasal
Attenuated Vaccine Duration of protection
Long-term
Types of Cells Created During Infection
Memory T and B Cells
Inactivated Vaccine Number of Doses
Multiple
Attenuated Vaccine Need for Adjuvant
No
Attenuated Vaccine Stability in Warm Temperatures
Poor
Memory cytotoxic T-cells
Result of encountering endogenous antigen, infected cells produce better T-cell responses
Definition of SARS-CoV-2
Severe Acute Respiratory Syndrome Coronavirus 2
Inactivated Vaccine Duration of Protection
Short-term
Memory B-cells and Th cells
The result of encountering exogenous antigen
Reason for Memory Cells
They can respond more quickly and strongly when the same (or similar enough) infectious agent is encountered again
Lung Tissue
Tissues within the body most impacted by SARS CoV-2
Dyspnea
Trouble Breathing
Attenuated Vaccine Number of doses
Usually Single Dose
Attenuated Vaccine Risk of mutation to virulence
Usually Very Low
Inactivated Vaccine Need for Adjuvant
Yes
Inactivated Vaccine Cell-mediated Immune response
poor
