Vaccine Development and Immunology Success Stories

Vaccine Development (Lecture + SGS)

• Rod Russell - Phase 2
• Objectives include describing how vaccination induces long-term immunity, the advantages and disadvantages of different vaccine types, and comparing/contrasting active, passive, therapeutic, and prophylactic vaccines.
• The plan involves a 30-minute lecture, a 20-minute exercise, and a 30-60-minute discussion.
• The promise of vaccines lies in specifically activating immunity for protection from infection or disease, achieving immunity without infection or sickness, and increasing safety through herd immunity.

Success Stories of Immunology

• Smallpox was globally eradicated in 1980, marking a major triumph.
• Polio eradication may be the next goal.
• The hepatitis B vaccine significantly decreased cancer incidence.
• COVID-19 vaccines are a recent success.

Why It's Difficult to Develop Useful Vaccines

• Influenza is an example, as a single virus type is responsible for most cases each year.
• Immunity develops mainly through antibody responses against viral proteins (HA), and also others (NA).
• Influenza virus exhibits antigenic variation through antigenic drift and antigenic shift.

Antigenic Variation

• Antigenic drift: Changes in epitopes of hemagglutinin in the influenza virus occur every 2-3 years, preventing existing antibodies from binding effectively. Ab and T-cell epitopes are affected.
• Antigenic shift: An infrequent but potentially pandemic event where RNA segments are exchanged between viral strains in different hosts. This leads to novel hemagglutinins, and no cross-protective immunity.

SARS-CoV-2 Antigenic Variation

• SARS-CoV-2 uses antigenic drift.

Types of Vaccines Used

• Live attenuated
• Whole inactivated
• Virus-like particles
• Subunit vaccines
• Live recombinant
• Conjugated
• DNA
• mRNA (with a question mark).

Remember Your Immunology

• Killed virus, recombinant, or purified protein vaccines stimulate antibody production through class II presentation.
• Live attenuated and live recombinant vaccines lead to intracellular infection, promoting class I and class II antigen presentation, and triggering antibody and cytotoxic T cell responses.

What is an RNA Vaccine?

• Pfizer and Moderna use mRNA in a nanoparticle delivery system.

Nanoparticle Delivery

• Nanoparticles are used as drug carriers in various therapies, including cancer treatments.
• They encapsulate drugs to reduce side effects with a variety of materials used (Carbon nanotubes, metal oxides, gold nanoparticle, etc).

Nanoparticles as Therapies

• Doxil: An anti-cancer drug (doxorubicin) encapsulated in a liposome that reduces side effects.
• Abraxane: A nanoparticle formulation of paclitaxel used to treat several cancers.

COVID-19 Vaccine Pipeline

• Data on vaccine types (mRNA LNP, mRNA LNP, Chimp Adeno 5, Human Adeno26, Protein SU), doses, cold storage requirements, efficacy, and specific variant impacts are provided.

Bivalent Vaccines

• Moderna and Pfizer are using bivalent formulations.
• These include original Wuhan and Omicron (BA.1, BA.4/BA.5) sequences.
• Data is in progress to determine long-term efficacy.

The Immune Response

• A primary immune response followed by a secondary response is described.
• Antibody levels wane over time, which is normal.

The Two Phases of the Immune Response

• Antibodies in the blood can prevent infection for 2-3 months.
• Memory B and T cells eliminate the virus long-term.

The "Vaccinated Vulnerable" Group

• Elderly and frail individuals, people with immunocompromised systems (genetic or acquired), and those battling or recovering from cancer can have dampened immune responses to vaccines and viruses.
• Recent data from Canada indicates a significant portion of the population over 60, did not experience COVID.

Are Vaccines Failing?

• Vaccines are not failing for preventing severe disease, but may not be completely effective at preventing actual infections.
• Graph data on Canadian COVID cases and deaths from 2020 to 2022 provide context.

Can we talk about Herd Immunity Yet?

• The criteria for herd immunity depend on specific end goals.
• Herd immunity can be achieved through vaccination and natural infections.

Burning Questions About COVID-19 Vaccines

• Key questions regarding COVID-19 vaccine effectiveness, mixing/matching, delayed dosing, effectiveness against variants, immune escape, and annual vaccine evolution are outlined.

Exercise: Design a COVID-19 Vaccine

• A COVID-19 vaccine design exercise is discussed.
• Different vaccine types (Live Attenuated, Live Recombinant, Whole Inactivated, Virus-Like Particles, Subunit Vaccines, mRNA Vaccine) are assigned to groups.
• The exercise demands answering vaccine design and production, testing, expected immune response, and safety concerns related questions.