July 2000
BETHESDA, Md. - One method to streamline the evaluation of vaccines is immunologic correlates of protection.
"The correlate of protection is simply a way to try and predict whether there is going to be any meaningful interference in protection," said Kathryn M. Edwards, MD, professor of pediatrics in the division of infectious diseases at Vanderbilt University School of Medicine in Nashville, Tenn. "If we can determine for each vaccine an amount of antibody or some measure of immune function that correlates with disease protection, then we can circumvent repeating many efficacy trials. We can simply use the fact that a specific vaccine induces a specific immune response to say that the vaccine should be protective."
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Edwards, who spoke here at the
International Symposium on Combination Vaccines, cited the example of the
Haemophilus influenzae type b (Hib) vaccine. "There appears to be an
amount of antibody that, in general, was associated with protection in the past
in the efficacy studies," she said. "So when vaccines are combined and the Hib
vaccine is able to meet or exceed that level of antibody, then the vaccine can
be licensed without doing efficacy trials." A second example is tetanus. "We
know how much antibody is needed for tetanus to be protective. If a vaccine
reaches that level of antibody the vaccine can be licensed," Edwards said.
One potentially confusing area is the role of T-cell memory responses. "In general, we measure antibodies in the blood after vaccinations because that is easier to measure than looking at specific T-cell responses or memory responses," Edwards said. However, "the actual antibody levels may be a surrogate for some other immune function that we are not measuring, but may still be reflective of protection."
Edwards also voiced concern that the Food and Drug Administration (FDA) may be "worried about licensing a vaccine in which the antibody responses are lower when vaccines are combined" vs. when they are given separately. "But if you have a very good correlate of protection, then that should make people more comfortable. Even though an antibody response is less, it is still protective."
Edwards has been involved in the establishment of correlates for several vaccines. "In order to generate immunologic correlates of protection, you need to conduct efficacy studies. Then you have to correlate efficacy with antibody responses," she said. "In general, the initial correlates of protection for various vaccines need to be determined in the large efficacy trials."
Shorter prelicensure periods and decreased costs associated with developing new vaccines are two benefits of using correlates of protection. Moreover, with the advent of multiple vaccines being administered together, "parents and doctors are really feeling very frustrated about giving four shots. A point will be reached when people won't want to give any more injections. This may ultimately sacrifice the effectiveness of our vaccination system," Edwards said.
"It is a delicate balance, though. We don't want to combine vaccines that are less effective or induce more reactions than when they are given separately. So we must proceed cautiously. But I believe in the hands of skilled investigators that the correlates of protection are very important and certainly should be pursued."
For more information:
- Edwards KM. Development, acceptance and use of immunologic correlates of protection. Presented at the International Symposium on Combination Vaccines. Feb. 2-4, 2000. Bethesda, Md.
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