Larson COVID Vaccines

What is the difference between positive-sense and negative-sense RNA viruses?

• Positive sense

  • RNA can act as mRNA → translate into protein

• Negative sense

  • RNA requires conversion to positive sense before translation

Characteristics of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)

• Highly pathogenic

• Enveloped, positive sense, single stranded, non-segmented RNA virus

How does SARS-CoV-2 enter cells?

• By binding angiotensin converting enzyme 2 (ACE2) receptor through spike protein (S)

• Endocytosis

Acute Respiratory Distress Syndrome (ARDS)

• Clinical feature of COVID-19 that can be fatal

• Monocytes and neutrophils are attracted to damage and promote inflammation and coagulation

  • Neutrophils, activated by platelets, release NETs and promote formation of microthrombi

Result of Acute Respiratory Distress Syndrome (ARDS)

Focal pattern of highly inflamed and flooded lung tissue, impairing oxygen exchange and leading to hypoxia

What was the overall goal of the Dan et al. COVID study?

To understand immune memory responses to SARS-CoV-2

What were the four types of immune memory examined in the Dan et al. COVID study?

• Antibodies

• Memory B cells

• CD4+ T cells

• CD8+ T cells

What does durability mean in the context of immune memory?

The length of time immune memory is measured after infection

Why is IgA important in the context of SARS-CoV-2 infection?

It is associated with humoral immunity at mucosal surfaces like the airway and lung, major sites of SARS-CoV-2

What functions do circulating T follicular helper (cTfh) cells serve as it relates to B cells?

• Provide B cell help

• Support SARS-CoV-2-specific antibody generation

• Long-lived humoral immunity

CCR6+ SARS-CoV-2-specific cTfH (circulating T follicular helper) cells increase over time. What is the function of CCR6? What might be happening to cTfh cells that express CCR6?

CCR6 is a chemokine receptor that mediates cell migration into tissue (especially mucosal tissue like lung and airway)

The increase in CCR6+ cTfh may indicate that these cells are migrating into tissues and providing support of local humoral immune responses

Immune memory to SARS-CoV-2 is heterogenous, which means _____

Different individuals have different patterns of immune memory

What percentage of patients retained immune memory ~6 months after infection?

95% of patients had at least 3 out of 5 immune memory responses at 6-8 months

Is durable immunity possible against secondary COVID-19 disease?

Yes (longer studies are needed to determine how long)

How do mRNA vaccines elicit an immune response?

1. Intramuscular immunization

2. mRNA/antigen uptake by APCs

3. Trafficking to lymph nodes

4. Priming of T lymphocytes

5. CD4 and CD8 T cell activation

6. Germinal center reaction

   • Produces MBCs (Memory B Cells) and LLPCs (Long-Lived Plasma Cells)

Janssen COVID Vaccine

Viral vector vaccine

A replication defective adenovirus that carries the gene for the SARS-CoV-2 spike protein

• Cannot replicate or cause infection

How does boosting (for COVID vaccine) work if it doesn’t match the new variants?

• Greater levels of and cross reactivity from neutralizing antibodies

• T cells are holding up really well against variants

• Leads to affinity maturation, which makes broader and more efficient antibodies

What is the “prototype pathogen” approach in the context of COVID vaccine development?

• Coronaviruses were known to have outbreak potential

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

• Developed and tested the mRNA platform before COVID19

What does it mean that mRNA vaccines are “plug and play”?

• Can modify for new strains

• Fast and easy to produce

• No infectious virus

How was the COVID vaccine developed so fast?

Overlap in early clinical trials phases and manufacturing

Safety benchmarks were NOT lowered by the FDA