David Lewinsohn
Working Group on New TB Vaccines

Hello, my name is David Lewinsohn. I am a human TB immunologist, a pulmonologist, and a professor of medicine at Oregon Health Sciences University. I'm also the Chair of the Stop TB Partnership Working Group for New Vaccines.

In this lesson, I'm going to walk through the stages of vaccine research and development starting with the first stages of research and going through to when vaccines are approved for use, also referred to as when vaccines are licensed or registered. You will also learn how the safety of new vaccines is monitored, even after they're being widely used.

Before we review the stages of vaccine development, I want to go over a few key concepts and definitions with you.

First, I'd like to define what we mean when we speak of vaccine candidates. We use the word candidate to refer to a vaccine that is undergoing research and testing, but has not yet been approved for use.

An important concept is vaccine indication. Indication refers to the specific goal the vaccine candidate has been designed to achieve. Sometimes a new vaccine may be able to achieve more than one specific goal. For new TB vaccines, potential goals include
preventing TB infection, preventing TB disease, or preventing recurrence of TB disease in people who have been treated for TB and who have made a full recovery. Additionally, a TB vaccine may be used to shorten the course of TB treatment or improve the outcomes of TB treatment, increasing the likelihood of a full cure.

In this module we will focus on vaccines indicated for preventing TB infection or preventing TB disease.

TB vaccines could be developed for one or several different target populations, including different age groups - for example, infants, adolescents and/or adults, people with TB infection or people who are not infected with TB and people living with HIV.

Another key concept is vaccine efficacy. Efficacy is a measure of how well the vaccine works in achieving the goal for which it was designed - it's indication - during clinical testing.

Another key concept is what we call the vaccine platform. The vaccine platform refers to the type of vaccine based on how it's structured and how it produces an immune response in the body. Some vaccine platforms used in TB vaccine development include
viral vectored vaccines protein subunit vaccines, and whole cell vaccines.

The next term is antigens. Antigens are key parts of a bacteria or virus against which the body generates an immune response. Vaccines contain antigens that will trigger an immune response that will achieve the goal or indication of the vaccine. For example,
preventing TB infection or preventing TB disease.

The route of administration is how a vaccine is given to a person. For example, the BCG vaccine is administered by an injection with a needle. Other routes of administration are being explored for new TB vaccines.

What I'd like to do now is to explain the stages of research. You can find a link to the overview of these stages in your module guide.

The first stage is discovery. In the discovery stage of vaccine research and development, scientists first seek to understand how the immune system can prevent infection or can prevent progression once infected. From here, scientists can develop a concept or idea
for a vaccine and determine what kind of vaccine could elicit these protective responses.

Keeping in mind the ultimate target indications and target populations, they select vaccine platforms, the antigens the vaccine will contain, the vaccine formulation, and the route of administration based on these considerations.

If, during the discovery phase, a vaccine candidate shows promise, it goes to the next stage, which is the preclinical development stage.
The preclinical research stage involves testing a vaccine candidate in animals, where the vaccine developers work to show that the vaccine can generate the intended immune responses, is protective, and assess whether the vaccine will be likely safe in humans.

If, in preclinical development a vaccine candidate shows that it is likely to work well and be safe in humans it moves to the clinical development stage, where vaccines are tested in human volunteers in clinical trials.

It's important to note that before a vaccine candidate can be tested in human volunteers, the plans to move into clinical trials must be approved by a regulatory agency. Regulatory agencies - like the Food and Drug Administration in the US, the European Medicines
Agency, or the South African Health Products Regulatory Authority - assess the vaccine candidate and the results of preclinical testing to determine if the candidate appears to be sufficiently safe and generates an appropriate immune response. If it does, then it can
advance to testing in people.

It is also important to note that all clinical trial protocols, the detailed plans for conducting the clinical trial, must be reviewed and approved by an ethics committee.