Exam 3- Lecture 7: COVID Vaccines

How were COVID vaccines developed so rapidly?

• Prototype pathogen approach

• Prior research in mRNA therapeutics

• Spike stabilization for virus vaccines

  • Better neutralizing antibody responses

• Overlapping manufacturing/clinical trail design

What tools were quickly used?

• Masks

• Ventilation

• COVID testing

• COVID therapies

• COVID vaccines

How do you make a vaccine?

• Conventional approaches

  • Whole virus vaccines

    • Attentuated virus

    • Inactivated virus

  • Protein subunit vaccines

  • Viral-like particle’s

• SARS-CoV-2

  • Spike

  • Novel approaches

    • mRNA vaccine

    • Non-replicating viral vector

What do we need from a COVID vaccine?

• Immunologically:

  • Antibodies against receptor binding domain (RBD) of spike protein

  • T cell responses to preserve memory

• Protection from disease is a must

  • Protection from transmission would be valuable

What is Moderna?

• mRNA vaccine for SARS-CoV2 spike protein

  • Modified sequence to make protein configuration more stable

• Encapsulated w/in a lipid nanoparticle

  • Protects RNA from degradation

  • Easily taken up by antigen-presenting cells

• NO LIVE VIRUS

What is Pfizer?

• mRNA vaccine

  • Similar formulation to Moderna

    • mRNA for spike protein w/ minor modifications

    • Uses a small number of modified uridines to increase mRNA stability & translation

  • RNA itself acts as an adjuvant

    • Our cells have sensors for viral RNA, which also respond to the vaccine

      • Helps to engage immune response

How do mRNA vaccines elicit an immune response?

1. Intramuscular immunization

2. mRNA/antigen uptake by APCs

3. Trafficking to lymph nodes

4. Priming to T lymphocytes

5. CD4 activation & CD8 activation

6. GC reaction

What is Novavax?

Protein Subunit Vaccine

• Produce spike protein insect cells

• Coat nanoparticles in spike protein

• Mix w/ adjuvant called Matrix-M

  • Made from sap of soap tree

What is Janssen?

A viral vector vaccine

• A replication-defective adenovirus that carries the gene for SARS-CoV2 spike protein

  • Cannot replicate or cause infection

• Backbone of current Ebola vaccine

• Low risk of thrombosis w/ thrombocytopenia syndrome (TTS)

  • 3.23 TTS cases per million doses administered

• Not available in US as of May 2023

What are common side effects of vaccines?

• On arm where you got shot:

  • Pain

  • Swelling

• Throughout rest of body:

  • Fever

  • Chills

  • Tiredness

  • Headache

What to do after shots?

• To reduce pain & discomfort where you got shot:

  • Apply clean, cool, wet washcloth over area

  • Use or exercise your arm

• To reduce discomfort from fever:

  • Drink plenty of fluids

  • Dress lightly

When should ibuprofen, aspirin, antihistamines, or acetaminophen be taken for vaccine pain?

• Okay AFTER vaccinatino

• Do NOT take before

What are COVID booster shots?

• Primary series were monovalent

  • Designed against original strain from 2019

• Bivalent booster introduced in 2022

  • Original stain +

  • Omicron subvariants (BA.4 & BA.5)

    • Provided significant protection against symptomatic infection, severe illness

• By Sept 2024, XBB variants accounted >99% of circulating strains

  • Protection from bivalent boosters started waning around this time

• Monovalent booster was introduced for 2023-34 that covered XBB variants

What is the current COVID booster?

• Modern & Pfizer (mRNA vaccines)

  • Designed against LP.8.1 strain

  • Novavax (subunit vaccine) is against the JN.1 strain, which dominated in 2024

• Preliminary data for 2025-26 suggests protection against severe illness, hospitalizations, & outpatient visits

How does boosting help?

• Greater levels of & crossreactivity from neutralizing antibodies

• T cells are holding up really well against variants

What are vaccine responses?

Polyclonal

• Our bodies make many different antibodies against spike proteins Cannot replicate

• Unlikely that a variant will interfere w/ ALL of those antivoides

  • But will evade some..

• Boosting leads to affinity maturation

  • Broader & more efficient antibodies

What was the COVID vaccine development?

• “Prototype pathogen” approach to vaccine development

  • Coronaviruses were known to have outbreak potential

  • Some labs studied SARS & MERS in anticipation of a new coronavirus

  • Developed & tested the mRNA platform before COVID19

• mRNA vaccines have been studied for nearly 20 years

  • LOTS of other clinical trial data (HIV, ZIKA, & others)

  • Phase 1 safety data already available

• mRNA vaccines are “plug & play”

  • Can modify new strains

  • Fast & easy to produce

  • No infectious virus!

How did our technology help COVID vaccine development?

• More advanced & specific

  • mRNA vaccines used a “stabilized” spike protein

    • Added 2 prolines

    • Held in a conformation that best elicits neutralizing antibodies

  • Approach was already discovered using MERS & Respiratory Syncytial Virus (RSV)

• Overlap in early clinical trial phases & manufacturing

• Safety benchmarks were not lowered by FDA

What is mRNA technology was/is being studied for?

• Influenza

• HIV

• Malaria

• TB

• Lyme disease

• Pancreatic cancer

• Sickle cell anemia

• Peanut allergies