Human serum albumin in vaccines comes from donated human blood plasma. Specifically, it is extracted from pooled plasma collected from thousands of screened donors, most of them in the United States. The albumin serves as a stabilizer in a small number of vaccines, appearing in tiny amounts (0.3 mg or less per dose) in products like the MMR and MMRV vaccines.
How Plasma Is Collected
About 85 to 90 percent of the plasma used for albumin production is collected through plasmapheresis, a process where a donor sits in a collection center while a machine draws blood, separates out the liquid plasma, and returns the red blood cells to the donor. The remaining 10 to 15 percent comes from “recovered plasma,” which is separated from routine whole blood donations.
The pooled plasma that goes into a single batch of albumin can come from thousands of individual donors. The majority of this plasma is collected in the United States, followed by China and Europe.
Donor Screening and Testing
Every plasma donation is tested for hepatitis B, hepatitis C, HIV, and syphilis before it enters the manufacturing supply. Donors are screened at each visit, and additional health monitoring occurs every four months, including protein testing to confirm the donor is healthy enough to continue donating. The FDA requires testing for a panel of bloodborne pathogens including HTLV (a virus related to certain leukemias) at each donation as well.
How Albumin Is Separated From Plasma
Raw plasma contains hundreds of different proteins. To isolate albumin, manufacturers use a technique called cold ethanol fractionation, originally developed in the 1940s. The process works by gradually increasing the concentration of ethyl alcohol in the plasma while carefully controlling temperature, pH, and protein concentration. Different proteins fall out of solution at each stage. Albumin is the most soluble of the major plasma proteins, so it remains dissolved the longest and appears in the final fraction, separated from antibodies and clotting factors that precipitate out earlier.
Modern facilities often combine this fractionation step with additional chromatography (a filtering technique that separates molecules by size or charge) to raise the purity of the final product. The result is pharmaceutical-grade albumin with purity around 98 percent or higher.
Viral Inactivation: The Pasteurization Step
After purification, the albumin undergoes a dedicated virus-killing step: pasteurization at 60°C (140°F) for 10 hours. This prolonged heat treatment inactivates both enveloped viruses like HIV and hepatitis B and harder-to-kill non-enveloped viruses like hepatitis A. Albumin’s molecular structure, reinforced by 17 internal chemical bonds called disulfide bridges, allows it to survive this heating while other proteins and viral particles are destroyed. This pasteurization step has been standard practice for decades and is one reason albumin has an extensive safety record as a blood-derived product.
Why Vaccines Use Albumin at All
Albumin acts as a molecular bodyguard for the active ingredients in a vaccine. It prevents the fragile viral proteins from clumping together, sticking to the walls of glass vials or plastic syringes, or breaking down from oxidation during storage. Without a stabilizer like this, the vaccine’s potency could drop before it ever reaches a patient.
Only a handful of vaccines actually contain human serum albumin. The two most common are MMR-II (measles, mumps, rubella) and ProQuad (measles, mumps, rubella, varicella), each containing 0.3 mg or less per dose. For perspective, your bloodstream naturally carries about 35 to 50 grams of albumin per liter, so the vaccine dose is a vanishingly small fraction of what your body already has circulating.
Regulatory Oversight
The FDA requires that human serum albumin used as a vaccine excipient be a U.S.-licensed product, meaning it has passed the agency’s own manufacturing and safety reviews. Manufacturers must document exactly which licensed albumin product they use, provide certificates of analysis, and demonstrate it meets quality specifications at every stage. If a manufacturer wants to use albumin that isn’t U.S.-licensed, the FDA expects a written justification explaining why.
Recombinant Alternatives
Researchers have developed ways to produce human albumin without using human plasma at all. Recombinant albumin is made by inserting the human gene for albumin into yeast, rice, tobacco, or potato cells, which then produce the protein through fermentation or plant growth. Yeast-based systems are the most established, but transgenic rice has drawn interest because production can be scaled up simply by planting more acreage rather than building larger fermentation tanks.
Recombinant albumin eliminates any theoretical risk of bloodborne contamination and removes the dependence on a limited donor supply. It is already used in some pharmaceutical and laboratory applications, though plasma-derived albumin remains the standard in currently licensed vaccines.