after vaccines are approved for use and includes the monitoring of adverse events

following immunization.

Vaccines are regulated by different, specialized branches within the public

regulatory bodies. As an example, the process for approval of vaccine in Canada is

presented in the following reference [16].

Safety and efficacy are first evaluated in animal studies or preclinical studies.

Afterwards, the four phases of the clinical studies are initiated:

Phase 1 studies a vaccine on a small group of people (usually fewer than 100) for the

first time, examining its safety including dosage range and side effects.

Phase 2 studies a vaccine on a larger group of people (usually several hundred or

more), to see how effective the vaccine is in preventing a disease, confirming its safety

and its optimum dosage.

Phase 3 studies a vaccine on a larger group of people (usually many thousands) to

confirm that it is both effective and safe by monitoring its side effects and any adverse

reactions.

Phase 4 occurs after the vaccine has been approved for use and is incorporated into

immunization surveillance programs. This is also known as post-marketing surveil-

lance. This includes ongoing safety monitoring, assessing vaccine effectiveness in

specific population groups, and determining the duration of immunity to inform future

decisions on the need for booster doses.

As it is the case for any biologics, any significant change in the vaccine manu-

facturing process might require clinical demonstrations of safety and eventually

efficacy. Manufacturing of vaccines on different sites or countries might require

bridging clinical trials. The role of the WHO through “pre-qualification” of vaccine

manufacturing sites worldwide is an improved process for facilitating commer-

cialization of vaccines in the different regions of the world.

1.5

BASIC PRINCIPLES OF VIRAL VACCINE DESIGN AND

TRADITIONAL PRODUCTION

This textbook focuses only on viral vaccines; therefore, although designed using the

same principles to activate immune response, other microbial infections and vac-

cination strategies will not be discussed. Vaccines might be classified taking into

consideration their design and mode of exposure of the dominant antigen to the

human immune system.

Figure 1.1 captures the principles of vaccination and provides a simplified

view of the possible interaction pathways with key mediators of the immune

response. This section will be detailed in Chapter 3 of this textbook by reviewing

the basic principles in immunology that are directly applicable to vaccine design

and development.

Traditional viral vaccines involve the whole virus as inactivated or live atte-

nuated, such as influenza vaccines (Chapter 9), or a sub-unit, representing the

6

Bioprocessing of Viral Vaccines