With much enthusiasm surrounding potential vaccines against COVID-19, it is important to understand the fundamental principles of vaccine protection. This article will briefly describe the major principles of vaccine protection.

Background Information:

Anamnestic response: A bodily defence reaction that recognizes an invading substance (an antigen: such as a virus/fungus/bacterium/transplanted organ) and produces specific antibodies against that antigen.

Example: In typhoid disease, antibodies may rise with other infections like malaria/ other fevers. If a child had a previous attack of enteric fever/ immunization with TAB vaccine, the H antibody titre rises rapidly with non-typhoid fevers, but the tires of O antibodies does not rise. This is called anamnestic (does not forget) reaction. High anti-H and low anti-O suggest anamnestic reaction.

Mechanistic correlation of protection: An immune response that is directly responsible for protection.

Non-mechanistic correlation of protection: An immune response that is easy to measure but which may only be a substitute for a mechanistic correlation of protection that is unknown or difficult to measure.

Co-correlates of protection: More than one immune function induced by a vaccine correlates with protection in an additive or synergistic manner.

Principles of vaccine protection

Principle 1: Protection must be defined in relation to specific phenomena

When one considers protection in the context of a vaccine-preventable disease, protection must be defined in relation to specific phenomena. In this context phenomena may refer to disease/infection, viraemia/ bacteraemia, prevention of carrier state, etc.

Protection against disease may relate to different immune markers than infection.

Example: Paralytic polio (disease) can be prevented by serum antibodies as the virus must pass to the central nervous system via blood. However, infection is prevented by antibodies at the mucosal level- either locally produced immunoglobulin A (IgA) antibodies or diffusion of IgG antibodies onto the mucosal surfaces of nasopharynx or intestine.

Principle 2: The mechanism of protection by vaccination is not necessarily the same mechanism as recovery from infection

The development of immunity after acquiring natural disease may involve a different immune mechanism than development of immunity after vaccination.

Example: A person requires both B and T cells to overcome naturally acquired vaccinia virus and become immune. However, in previously vaccinated individuals only neutralizing antibodies are required for protection (at levels between 1/20 and 1/32). Although antibody titres decline by 20 years after vaccination, the presence of antipoxvirus T cells enables the vaccinee to have a mild secondary infection in case of exposure.