In the 1950s, 3 to 4 million people got measles every year in the United States. Scientists developed a vaccine for the highly contagious respiratory disease in 1963, and by 2000, the disease was effectively eliminated from American soil. But unvaccinated people continue to contract the disease. A particularly bad outbreak occurred in Ohio’s Amish country last year, infecting more than 300 unvaccinated people, and an exposure incident at Disneyland in California last month has already infected more than 100 people in 14 states, mostly children whose parents do not believe vaccines are safe.
Pharmaceutical company Merck manufactures the measles vaccine in the United States. Each vaccine also includes inoculations against the mumps, another contagious disease, and rubella, also known as the German measles. Each 0.5-milliliter dose of the combo vaccine, known as MMR II, contains 10 ingredients. We chatted with Vincent Racaniello, a professor of microbiology and immunology at Columbia University, to find out what exactly those ingredients are and what they do. Racaniello has worked with viruses for the past 35 years.
To make a vaccine against a disease, which is caused by a virus, scientists first must grow it in a lab. “Every vaccine is different, but they all basically start as cells growing in a plastic dish with a liquid medium on top,” Racaniello says. “The cells are infected with the virus and over the course of a few days, the virus grows. Scientists harvest the medium on top of the cells, where the virus is, and that’s what they use for the vaccine.”
The strain of measles used for the measles vaccine, known as Edmonston, is derived from the original 1960s vaccine. Scientists use chick embryo cells to culture the virus. The liquid growth medium on top is known as Medium 199, a salt solution that includes vitamins, amino acids, and fetal bovine serum, plus sucrose, phosphate, glutamate, neomycin, and recombinant human albumin (more on those ingredients below).
Mumps is grown the same way as measles: in chick embryo cell cultures and with the Medium 199 liquid growing medium.
Unlike the measles and mumps, rubella is grown on cells from human diploid lung fibroblasts, known as WI-38. “This is a cell line that has been around for many years,” Racaniello says. “It was done once and then these cells keep growing in cultures forever. You keep them in your freezer in your lab. So you don’t have to get a human lung every time you make a vaccine.”
Rubella is grown in Minimum Essential Medium, a salt solution that contains vitamins, amino acids, and fetal bovine serum, plus recombinant human albumin, and neomycin.
Sorbitol is a stabilizer. It is also used as an artificial sweetener in food. “It’s added to the vaccine to keep the viruses from falling apart as they’re handled,” Racaniello says.
Sodium phosphate, or salt, is used as a buffer to maintain the vaccine’s pH level when it is frozen or thawed. “Vaccines are provided [to hospitals and doctors from the manufacturer] frozen,” Racaniello says. “They are frozen until they need to be used. When you thaw them, sometimes the pH can change and that would not be good for the infectivity. Often even in a frozen state the pH will change, but especially when you thaw it. Sodium phosphate, the buffer, maintains it at pH 7, which is where they want to keep it.”
Sucrose, or sugar, is a component of the liquid growth medium that the cells were originally grown in. Sucrose is the cells' energy source. “The growth medium provides the cells with the nutrients they need,” Racaniello says. “It has a variety of things in it, including sucrose, and because we make a vaccine out of that medium, those components are also present in the vaccine.”
Sodium chloride, another salt, is also from the cell culture medium. “It’s there to make sure the medium is isotonic,” Racaniello says. “Cells have a certain amount of salt in them and the medium has to match. It’s just like when you get an intravenous drip and they use a saline or sodium chloride solution that matches the composition of your body fluids. This is here to match the composition of the cells on which the viruses are grown.”
Like sorbitol, hydrolyzed gelatin is a stabilizer to make sure the viruses stay infectious. “Gelatins are long chain molecules,” Racaniello says. “Hydrolyzed means it has been broken up into smaller components and that makes it more effective as a stabilizer.”
Recombinant Human Albumin
This protein is another component of the cell culture medium, which helps the cells grow properly. “Human albumin is found in blood,” Racaniello says. “Recombinant means it is made in a highly purified manner without contaminants.” To make the albumin, scientists put a gene for a human albumin in a cell and grow it in a lab. Once the cell produces the albumin, scientists can collect it and purify it directly from there, as opposed to stripping it directly from a blood sample, which could contain many contaminants.
Fetal Bovine Serum
Fetal bovine serum, which is collected from cow blood, is also a carry-over from the cell growth medium. “It’s very rich in growth factors,” Racaniello says. “We actually don’t know all of the different factors that are needed for cells to grow and culture. Otherwise we could make them in a lab and mix them all together. That’s why we still use serum from an animal to do that.”
The vaccine’s ingredients include items that help it grow in the lab and help keep it together in a vial. So what happens to them once they’re injected into your body?
The MMR vaccine is typically injected subcutaneously, where it begins to diffuse into your tissues and reach the lymph system. “The lymph system is composed of very permeable capillaries that take up anything that’s floating around in the tissues,” Racaniello says. Next the vaccine would enter a lymph node, which is a collection of immune cells. When the immune cells detect a foreign product such as the viruses contained in the vaccine, there is usually an immune reaction. “If you get a shot in the arm and you get sore, that’s because you’re having a little immune reaction to the components,” Racaniello says. “That’s actually good because it tells you that it’s working.”
Eventually the virus would spread throughout your entire body. “These are infectious viruses, so they would replicate in certain kinds of cells and produce more viruses, which would give you a really good immune response,” Racaniello says. “That’s why the vaccines work so well; because they’re infectious viruses.” Those viruses that your body produces will not give you measles or mumps or rubella, but they will alert your immune system to start making antibodies to defend against them. Then, if you ever got infected with measles or mumps or rubella, those antibodies would be there to block infection.
As for the other components, they diffuse throughout your entire body within a few minutes. “All of those things get immediately diluted so you wouldn’t have any sense that they’re there anymore,” Racaniello says. “Vaccines are great. They prevent diseases. This one has been used for a long time and it’s really unfortunate that people aren’t using them as much as they should. These infections can be lethal.”