Viral Vaccines: Principles and Properties

Viral Vaccines

• Vaccines are biological preparations which provide active immunity to an infectious disease.
• Immunization is the process where a person becomes protected from a specific disease after being administered a vaccine.
• Vaccination is the injection of a killed/weakened organism which then produces antibodies (immune response) against a particular infectious agent.
• Antigens cause the immune system to produce antibodies against them.

Principles of Vaccines

• Vaccinations mimic the first exposure which occurs with natural infection.
• Antibodies are produced against the organism during the first exposure.
• The second exposure results in a more rapid and vigorous response
• Increased immune response leads to, lowered viral replication and in turn less disease

Ideal Vaccine Properties

• Inexpensive
• Stable
• Easy to administer
• Effective
• Safe
• Provides long-term protection
• Creates Mucosal and Systemic Immunity
• Has Cell-mediated and Humoral Immunity
• Is Cross-reactive against all subtypes/strains

Benefits of Vaccination

• Protection against disease and/or long-term sequelae or death for the individual.
• Provides herd immunity
• Results in eradication/elimination of disease, as seen with Smallpox

Herd Immunity

• Is the protection afforded to non-immune individuals due to interruption of chain of transmission by immune people, either through natural immunity or the vaccine.
• Immunization leads to decreased cases of communicable diseases.
• Immunization leads to decreased hospitalization
• Immunization leads to decreased deaths

Limitations of Vaccines

• Can cause side effects, which are usually minor.
• Has a delayed response as vaccines are not immediately effective. Immunity takes ~ 2 weeks to develop
• Requires a competent immune system. It may be less effective in immunocompromised hosts).
• Some require boosters (more than 1 dose).
• Maternal antibodies may neutralize some vaccines.
• Aren't 100% effective.
• Some only protect for a few years.

Common Vaccine Side Effects

• Injection site reactions (pain, swelling, and redness) are the most common.
• Mild fever, headache, muscle aches, irritability/crying in babies, vomiting and diarrhea
• Rare side effects include seizures, high fever, and rash.
• Allergic reactions can occur; anaphylactic reaction: 1 in a million cases.

Attenuated Vaccine Side Effects

• Reversion to "wild-type" is possible.
• Milder form of natural disease such measles, a full-blown disease (in immunodeficiency) and fetal infection (in pregnant women) are possible results.

Types of Vaccines

• DNA and RNA vaccines use DNA or RNA molecules so that the immune system can target viral proteins.
• Live attenuated vaccines use a weakened version of the actual virus to stimulate.
• Inactivated vaccines use the whole virus after it has been killed with heat or chemicals.
• Subunit vaccines use a piece of a virus' surface.
• Viral vector vaccines use a harmless virus and uses it to deliver viral genes to build immunity.

Advantages and Disadvantages of Vaccine Types

• DNA and RNA: Easy and quick to design; but can have rare serious side effects
• Live attenuated: Stimulates a robust immune response without causing serious disease. May not be safe for those with compromised immune systems
• Inactivated: Safe as viruse is already dead and is easy to make; but is not as effective as a live virus. Safety for the novel coronavirus still needs to be shown in clinical trials.
• Subunit: Focuses immune response on the most important part of the virus for protection and cannot cause infection; however, It may not stimulate a strong response, other chemicals may need to be added to boost long-term immunity.
• Viral vector: Live viruses tend to elicit stronger immune responses than dead viruses or subunit vaccines; but it's important to pick a viral vector that is truly safe. The vaccine could be less effective if a response to the viral vector occurs.

Attenuated vs Inactivated Vaccines

• Attenuated vaccines elicit a Cell-mediated +antibody response with long-lived immunity; while inactivated only elicit a predominant antibody response that may require booster doses and adjuvants
• Attenuated vaccines are contraindicated in severely immunocompromised patients and have a risk for Reversion to virulence; Inactivated vaccines are non-infectious
• Attenuated vaccines require specific storage conditions and must remain viable; inactivated vaccines are less sensitive

Reassortant Virus Vaccines

• Are designed to contain genes from both pathogenic virus + heterologous virus
• Contain only essential + 'immunogenic' genes that allow replication and induction of immune response.
• Omit Pathogenic' genes from chimeric virus

Vaccination Strategies

• Routine Immunisation (EPI-SA)
• Mass Immunisation (administration of vaccine doses to a large population over a short period of time for COVID-19)
• Mopping Up (door-to-door immunizations that are carried out in specific areas where the virus is suspected to still be circulating)
• Outbreak Response (vaccine as a tool to contain an outbreak)
• Eradication (Measles and polio are targeted)

Individual Vaccination Strategies

• Include Traveler vaccines (hepatitis A, Japanese encephalitis, yellow fever)
• Medical indications, (increased risk of complications e.g. influenza in patients with lung disease)
• Occupational risk (hepatitis B)
• Post exposure (rabies following dogbite, hepatitis B following needle-stick injury)

Passive Immunisation

• Is where Administration of a component of the immune system (e.g. antibodies) is given to prevent disease .
• The effect is immediate but temporary i.e. the antibodies work as soon as they reach effective tissue concentration, but the effect diminishes as concentration of the antibody wanes.

Passive Immunotherapy Examples

• Hepatitis B Virus immunoglobulin given to susceptible healthcare worker following needlestick injury (PEP) or a neonate born to sAg+ mother infected with hepatitis B virus (PrEP/PEP).
• Rabies immunoglobulin given following bite by suspected rabid dog (PEP)
• Zoster immunoglobulin given to susceptible pregnant women exposed to person with chickenpox
• Respiratory Syncytial Virus (RSV) immunoglobulin given to prevent RSV in high risk infants (PrEP)