News & Views: Making Sense of Immunogenicity and Efficacy Data in Vaccine Trials

• Immunogenicity – a measure of the immune response generated after a person is vaccinated.
• Efficacy – a measure of the decrease in likelihood of getting infected with or developing a disease after being vaccinated.

Immunogenicity and efficacy may be used interchangeably in conversations about vaccination; however, they are not exactly the same thing. This is especially true when discussing or interpreting data from vaccine trials.

Immunogenicity usually comes first

Typically, the first clue as to whether a vaccine works is provided by measuring the immune response initially in experimental animals. Immunogenicity can be defined by any of the aspects of the immune response that are measurable. Most often for vaccines on the market, the measures are of antibodies in the blood, but in the research lab, measures can include newly formed or memory B cells, antibody secreting cells, or killer T cells to name a few. For some diseases, scientists know from previous work with the disease that if a person has a high enough level of one of these immune system components, he or she will be protected; this is called a correlate of protection.

Example: Someone with 15 international units (IU) of rubella-specific antibodies in the serum is considered to be protected against rubella. This is known as a correlate of protection.

If a correlate of protection is known and the potential vaccine does not induce a potent enough immune response, scientists need to reconsider the vaccine composition, dosage, and number and timing of doses. These studies can take years and are most often done in animals.

Unfortunately, for many diseases a clearly defined correlate of protection is not known. This is particularly true with infections that occur at mucosal surfaces (nose, throat, lungs, intestines and anogenital areas). In these cases, the most useful information comes from comparing the levels of the immune response following vaccination to those in individuals with disease.

• When measuring immunogenicity, typically the higher the numbers, the better the protection because they indicate a stronger immune response.

But does the vaccine work?

While immunogenicity is helpful in assessing whether a vaccine is likely to work, it does not completely answer the question about whether the vaccine actually does work. That is, will a person who got vaccinated be protected if he or she is exposed to the disease? Efficacy data provides this information. As with immunogenicity, when researchers measure efficacy, they can measure a few different things. Most often they look at mild, moderate and severe disease which identifies everyone who gets ill, but by classifying severity of disease, the findings provides additional information about how the vaccine works. In cases of mild or moderate disease, the vaccine worked by altering the course of disease, and likely prevented some deaths, so it could still be considered valuable.

• When measuring efficacy, less is more because the lower incidence of disease in vaccine recipients compared with unvaccinated people means the vaccine worked.

Revisiting immunogenicity

So, now you might be wondering why we still hear about immunogenicity data if efficacy data better defines how well a vaccine works. The answer is for a few reasons:

• Correlate of protection — If a correlate of protection is known for the disease, researchers can be confident that a vaccine candidate inducing an appropriate level of immunity will work, so they do not need to necessarily measure rates of disease.
• Ethics — It would be unethical to knowingly make someone sick just to see how well a vaccine works. Imagine giving some people an Ebola virus vaccine that we do not know works and then introducing Ebola virus into the community to compare the rate of vaccinated versus unvaccinated people who get ill. If the disease is common or the risk is high, such as polio in U.S. communities in the 1950s or currently, Ebola in parts of Africa, people who volunteer for a vaccine trial are taking a chance that it doesn’t work, but they are also increasing their chance to avoid the disease.
• Opportunity — After a vaccine is on the market, rates of disease typically decrease in a community, so comparing a newer version of a vaccine would be more difficult to do. In addition to being unethical —recipients might not be as well protected as if they got the vaccine that already exists —the chance of either group being exposed to the disease is smaller, so getting enough data to determine efficacy could prove arduous. However, researchers can compare the immunogenicity that develops after receipt of the new product with that of the existing product. If immunogenicity is similar between the two groups (new vaccine versus old vaccine), researchers can conclude that the new vaccine works. Further, if the new vaccine responses are low, they can still offer the superior product to those who were in the trial if it is deemed necessary for their protection.

Summary

Immunogenicity and efficacy data provide information on how well a vaccine works, but they are not the same. So, if you are reviewing or explaining data, it is important to determine how the study was designed and what it measured in order to appropriately interpret the data.