Fetal bovine serum is the most widely used growth supplement added to eukaryotes in vitro cell cultures. It has been in use since the 1960s and, for over fifty years, has outperformed both synthetic and natural growth supplements.
In the fetal bovine serum collection process, blood is harvested aseptically via cardiac puncture and allowed to clot at cold temperatures. It is then spun in a centrifuge to remove specific cells, fibrin, and clotting factors. FBS is heavily regulated, especially in the cattle industry, and for good reason.1 Each batch of FBS is run through several filtration processes, kept refrigerated, and rigorously tested. FBS used in specific concentrations can satisfy special metabolic requirements and promote the growth of cells.
Fetal bovine serum (FBS) has many uses in both academia and industry and is commonly used in cell cultures for investigations into vaccine research and manufacturing. Read on to discover an explanation of what viral vaccines are, how cultured cells are being tested, and the role of fetal bovine serum in vaccines.
What are vaccines?
Before the modern scientific landscape, pattern-seeking and trial and error were the tools of human advancement. Evidence suggests that the Chinese used inoculation as far back as 1000 CE.1 Ayurveda texts from India also indicate the use of inoculation, and by the 1500s it was used in Africa and Turkey. Pandemics and epidemics2 were the most prolific killers of homo sapiens until the introduction of vaccines.
In an oversimplification, vaccines are a weakened or dead form of a disease-causing microorganism that stimulates the immune system and creates antibodies that protect against stronger versions of the pathogen.
The credit for modern western human vaccination is attributed to Edward Jenner, who in 1796 took pus from a milkmaid suffering from cowpox and infected eight-year-old James Phipps with the disease. Six weeks later, after James had recovered from cowpox, Jenner variolated the boy with smallpox, which never presented.
However, the use of cowpox inoculation did not become common until the 1840s.
The famous Louis Pasteur introduced the second generation of vaccines in the 1880s. Whereas Jenner’s breakthrough came about with the realization that those who survived cowpox were immune to smallpox, Pasteur, considered one of the fathers of germ theory, was the first to artificially weaken a disease and create a vaccine.
Starting in the late 19th century, researchers were looking to develop vaccines for both humans and animals, and sought to make and manufacture them in more or less a true environment—be it human or animal. Over the years, researchers explored a variety of avenues to reach this goal, including chemically-defined media, reduced serum type media and others, in order to find what provided the greatest efficacy.
Judy Pogoda-Leone, a Senior Manager of Technical Affairs who has worked within the Global Sera program at Thermo Fisher Scientific for over 35 years, describes how in this pursuit, researchers continued to return to FBS. “If you’re looking to get the best outcome from vaccines from a manufacturing-production perspective, FBS has provided the extra nutrients to be able to produce that vaccine. It’s not to say that folks are still not continuing to look at synthetics, but based on history and efficacy over the last 30 years, FBS is still a clear component of vaccine manufacturing.”
Cell culture media is arguably the most critical factor in cell culture technology and thereby plays an important role in vaccine development. Here is a brief look at the history of cell culture as well:
- The earliest growth media were balanced salt solutions that used inorganic materials. Sydney Ringer, in 1882, developed Ringer's Solution, which was quickly followed by people inventing their own solutions.
- Natural media wasn't successfully used till 1908 by Margaret Reed (Guinea Pig bone marrow) and then by Alexis Carrel and Montrose T. Burrows, who used Plasma and other organic fluids as a media to grow mammalian somatic cells.
- The establishment of cell lines in the 1940s (the famous HeLa cells, for example) allowed researchers to have a homogenous population of cells on which to run experiments.3 This allowed for precise measurements of the effects of different culture media.
- The next few decades received tons of research on basal media, protein-free media, serum-substitutes, serum-free media tailored to cell type, improvements in basal media, and several other scientific inquiries.
Is fetal bovine serum used in vaccines?
Now with an understanding of the history, what does fetal bovine serum do and how is it used in vaccines?
Understanding that FBS is used as a supplement in growth media and that cultures are vital for research purposes (as well as for proliferating cells), the efficacy of FBS in vaccine development has been proven time and time again. FBS used in concentrations between 2-10% is highly effective in promoting growth in vitro cell cultures due to their nutritional, hormonal, growth, and attachment factors. FBS also has lower growth-inhibiting factors (like antibodies) and acts as a buffer towards changes in the environment (like pH shifts).
Thus, many human vaccines are prepared using fetal bovine serum as a supplement in their growth media.
Most often, FBS is used as part of the growth medium in which vaccines are studied, grown, and harvested. FBS doesn’t actually exist within the final vaccine itself; rather, its macromolecular proteins are used as nutrients, and other growth factors allow for the rapid proliferation of the desired cells.
Strict guidelines set forth by global government agencies (i.e. FDA, DEFRA, ANVISA, etc.) exert a high measure of quality control on FBS products.4 Disease status of animals are monitored by the World Organization for Animal Health (OIE).
Thermo Fisher Scientific has incorporated extra measures in order to help ensure the integrity of its FBS products. One such method is the fingerprinting technology used to determine and confirm the origin of the FBS. This helps the customer confirm the origin of the product they’re purchasing. Judy notes the importance of this, “when manufacturers are producing vaccines or other types of drugs, it’s important for them to confirm the origin, especially when doing submissions to the FDA or other regulatory authorities globally.”
Chris Scanlon, Market Development Manager within the FBS program described more about the fingerprinting technology, which was developed in conjunction with Oritain. “We worked with Oritain to design the fingerprinting technology for FBS with the goal of establishing it as an industry standard with the ISIA. In our development of the technology, we felt compelled to share it and develop it as a standard because we wanted everyone to have the same standards for origin confirmation. We take a lot of pride in helping not only our area of the business, but the industry as a whole.”
Fetal bovine serum has been used in vaccine production for over 50 years, and it has proven itself as an extremely effective growth supplement. Although customers would ideally prefer to be in a world where serum is synthetic, there is currently still a long runway until we reach that point. Chris Scanlon notes, “We’ve invested a lot of money and time to try to break that code and figure out a true synthetic. Our cell biology team has spent years trying to figure this out. However, until then, customers know that there is really no other alternative that works as well as FBS. It’s known as the ‘Golden Nectar of Reagents’ because it’s such a prolific reagent in research.”
- Hawkes, P.W. Fetal bovine serum: geographic origin and regulatory relevance of viral contamination. Bioresour. Bioprocess. 2, 34 (2015) doi:10.1186/s40643-015-0063-7
- Tatsuma Yao, Yuta Asayama. Animal‐cell culture media: History, characteristics, and current issues. Reproductive Medicine and Biology. 2017; doi:10.1002/rmb2.12024
For Research Use or Further Manufacturing Use only. Serum and blood proteins are not for direct administration into humans or animals.