Vaccine Types and Development

- Overview

There are many approaches to vaccine development, but vaccines can be broadly classified by how the antigen(s), the active component(s) that generate a specific immune response against the disease-causing organism, are prepared. Vaccines may be viral (live or inactivated), viral vector, subunit (protein or polysaccharide) or nucleic acid (DNA or RNA). Combination vaccines may include inactivated, protein-based and/or protein-conjugated polysaccharide vaccine components. Other ingredients in vaccines vary depending on the manufacturing process and the nature of the antigen(s). 

There has been an increased focus on vaccine development using the viral-vector and nucleic-acid based platforms since the appearance of the SARS-CoV-2 virus and COVID-19 disease in late 2019.

- Vaccine Development and Manufacturing

The first human vaccine against a virus is based on using a weaker, or attenuated, virus to generate immunity without giving the vaccine recipient full-blown disease, or preferably no symptoms at all. For example, the smallpox vaccine uses vaccinia, a poxvirus very similar to smallpox, that protects against smallpox but usually does not cause severe disease. Rabies was the first virus to be attenuated in a laboratory for use in a human vaccine.

Vaccines are manufactured using a variety of processes. They may contain live attenuated viruses (weakened or altered so as not to cause disease); inactivated or killed organisms or viruses; inactivated toxins (for bacterial diseases in which the toxin is produced by the bacteria rather than the bacteria themselves ); or simply fragments of the pathogen (this includes subunit and conjugate vaccines). 

The live attenuated vaccines currently recommended as part of the U.S. childhood immunization schedule include vaccines against measles, mumps, and rubella (via the combined MMR vaccine), varicella (varicella), and influenza (the seasonal flu vaccine nasal spray). Except In addition to live vaccines and attenuated vaccines, the immunization program also includes various major types of vaccines.

Vaccine development is difficult, complex, highly risky, and costly, and includes clinical development, process development, and assay development. The risk is high because most vaccine candidates fail in preclinical or early clinical development and less than 1 in 15 vaccine candidates entering Phase II achieves licensure. The high failure rate is the result of a variety of reasons:

• Not fully understanding the biology of protection.
• Lack of good animal models to predict vaccine behavior in humans.
• Unpredictability of human immune system reactions to antigens as it relates to immunogenicity or safety.
• The unpredictability of the impact of combining multiple components in a vaccine.

• When scientists develop a vaccine, they consider:
• How Your Immune System Responds to Germs
• Who Needs Bacterial Vaccinations
• The best technology or method for making a vaccine

Based on some of these factors, scientists decide which type of vaccine they will make. There are several types of vaccines, including:

- The Target Product Profile (TPP)

Vaccine development requires strong project management systems and controls and requisite skill sets among scientists and engineers. A key strategic document that guides the stakeholders in vaccine development is the “target product profile” (TPP). 

The TPP summarizes the desired characteristics and features of the product under development, the key attributes of the product that provide competitive advantage, and, finally, a topline roadmap of nonclinical and clinical studies required to evaluate the products efficacy and safety in the target population. A well-defined TPP provides all the stakeholders, including research, process development, manufacturing, clinical, regulatory, and senior management, with a clear statement of the desired outcome of the product development program.