An unusual and unexpected virus protein has been found in minute quantities in measles-mumps-rubella vaccine, but the scientists studying it don't believe it poses any hazard to people getting the immunization shots.
The protein, called reverse transcriptase, almost certainly comes from the remnants of ancient viruses that have been "preserved" for eons in the chromosomes of chickens. Chicken cells are used to make many vaccines, including the one in which the protein was found. There is no evidence that whole copies of the ancient viruses are in any vaccine.
"Based on the data we have so far, we believe the vaccine should be on the market, and people should continue immunizing their children," said Kathryn Zoon, head of the Food and Drug Administration's office in charge of vaccine safety.
"We are not investigating a situation in which there has been any adverse reaction at all," said Brian W.J. Mahy, director of the branch of the Centers for Disease Control and Prevention (CDC) that studies viruses.
The measles-mumps-rubella vaccine used in the United States is made by only one manufacturer, Merck & Co. Inc. However, the reverse transcriptase (RT) protein has been found in similar vaccines made by European companies, as well as in yellow fever and some influenza vaccines. All are prepared in chicken embryo cells.
Merck each year sells about 12 million doses of the vaccine (often abbreviated MMR) in the United States. MMR is given to children soon after their first birthday, and again when they are either about 4 or 11 years old. About 450 million doses of the Merck vaccine have been sold worldwide since it was introduced 24 years ago, a company spokeswoman said yesterday.
The World Health Organization estimates that measles vaccine prevents about 90 million cases of the disease annually, and about 1.5 million deaths.
RT is most commonly associated with retroviruses, a class of virus that can permanently alter the genes -- and consequently the behavior -- of cells they infect. The AIDS virus is the best-known retrovirus, although there are others that cause diseases, such as leukemia.
The discovery of RT in batches of MMR in June immediately raised the possibility that a complete retrovirus might somehow be contaminating the vaccine. The presence of the protein was detected by Swiss researchers using a new test that is a million times more sensitive than its predecessor.
Chicken proteins are normally found in many vaccines. No whole retrovirus, however, has been found in any vaccine samples. Furthermore, experiments done with Merck's chicken embryo cells -- the presumed source of the RT in that company's vaccine -- have not uncovered any virus capable of passing from chicken cells to human cells when the two are grown together in the laboratory.
Measles, mumps and rubella (also known as "German measles") all are caused by viruses (though none is a retrovirus.) The vaccine contains a functional, though weakened, measles virus, mumps virus and rubella virus. When a person gets the shot, the viruses infect human cells, causing a protective immune response that persists for years. But because the incoming virus is weak, the vaccine recipient experiences little or no illness.
To make such "live" vaccines, chicken cells are infected with virus, where the invading microbes grow, eventually bursting the cells and releasing millions of progeny. The vaccine given to people contains small quantities of the chicken cells' contents -- mostly a hodge-podge of different proteins. Now it appears RT is one of them.
Scientists at Merck Research Laboratories, outside Philadelphia, are attempting to figure out the location and origin in chickens of the RT gene that instructs the chicken cells to make the RT protein. According to Alan Shaw, head of the company's team working on the problem, there are four possibilities.
One is that the RT gene is in an "avian leukosis virus" (AVL), a retrovirus that infects some birds and can cause a leukemia-like illness. The Merck chicken flock has been kept in isolation and fed sterile feed since 1962, and is frequently tested for AVLs, which never have been found, Shaw said.
Second, all chickens have a few "proviruses" stitched into their chromosomes. These are the genes of retroviruses that infected the species eons ago. The Merck chickens carry two proviruses, one of which may contain a gene for RT.
A third source of the gene may be a related phenomenon, called "endogenous avian viruses." They are even more ancient viral remnants and appear to be carried by all birds, not just chickens. Some of these leftover genes may encode RT. This is the most likely source of the RT in vaccines, Shaw said.
The fourth possibility is that a few "retrotransposons," a form of mobile or "jumping" gene, may contain RT, again left over from primordial virus infections.
RT's main function is to copy a substance called RNA into DNA, the biochemical that permanently stores genetic information. The RT from chickens requires a specific primer, a particular short segment of DNA, to do this work. That primer is lacking in human cells, Mahy said, so it's virtually impossible the chicken protein could function in human cells.