Painkillers May Kill Vaccine Response

ROCHESTER, N.Y., Nov. 29 -- Reaching for a painkiller after a vaccination may be a bad idea, according to researchers here.

The cyclooxygenase inhibitors -- including aspirin as well as Celebrex (celecoxib) -- may reduce the antibody-producing effect of the vaccine, making it less useful in preventing disease, said Richard Phipps, Ph.D., of the University of Rochester School of Medicine and Dentistry here.

That's because one of the Cox enzymes -- Cox-2 -- is crucial for optimal antibody production, Dr. Phipps and colleagues reported in the December issue of the Journal of Immunology. Medications that block Cox-2, which is also responsible for the pain of inflammation, "may therefore reduce vaccine efficacy," the researchers said.

"We believe that when you reach for the medicine cabinet to reduce pain at the injection site, that is probably the wrong thing to do," Dr. Phipps said in a statement.

He added that more research is needed to see if timing plays a role in the effect. "The next step is to figure out the worst time to take drugs that inhibit Cox-2 in the context of getting vaccinated," he said. "Is it the day before, the day of, or the day after?"

The research is based mainly on an animal study, in which the researchers examined what happened to antibody production after vaccinating mice that are unable to produce Cox-2. Also, Dr. Phipps and colleagues studied stored blood samples of people who took part in early clinical trials of the vaccine against human papillomavirus (HPV).

The mice were vaccinated with a model vaccine against HPV-16, one of the strains of the virus that causes cervical cancer in humans. Compared to normal mice given the same vaccine, the Cox-2-deficient animals produced:

• 70% less anti-HPV 16 immunoglobulin
• 50% fewer antibody-secreting cells
• A 10^th of the neutralizing antibodies to HPV 16.

The key to the response may be B-memory cells, which Dr. Phipps and colleagues have shown also express Cox-2. In the Cox-2 deficient mice, fewer B-memory cells responded to the vaccine challenge, compared to the normal mice, they found.

To confirm that finding in a human context, the researchers examined stored blood samples from volunteers vaccinated against HPV 16 in early clinical trials. When re-stimulated, the B-cells in the samples produced an antibody response against the virus, but adding a Cox-2 inhibitor blocked the response in a dose-dependent fashion, Dr. Phipps and colleagues reported.

Co-author Robert Rose, Ph.D., said the study does not call into question the efficacy of the recently approved multivalent HPV vaccine, which has been shown in clinical trials to provide protection against cervical cancer, because presumably many of the participants in the studies were also taking non-steroidal anti-inflammatory drugs (NSAIDs) at the time.

"Still, our data does suggest that it might be wise to limit the use of NSAIDs when you receive any vaccine," Dr. Rose said in a statement. He was one of the developers of the HPV vaccine.

The finding may also partly explain the poor response of the elderly to vaccines, Dr. Phipps said, because they are more likely to be taking painkillers of various kinds than are younger people.

"For years we have known that elderly people are poor responders to the influenza vaccine and vaccines in general," he said "And we also know that elderly people tend to be heavy users of inhibitors of cyclooxygenase, such as Advil, aspirin, or Celebrex. This study could help explain the immune response problem."