What Is a Vero Cell Vaccine and How Is It Made?

A Vero cell vaccine is any vaccine whose viral component is grown inside Vero cells, a laboratory cell line originally derived from the kidney of an African green monkey. These cells have been a workhorse of vaccine manufacturing since the 1980s, used to produce everything from rabies and polio vaccines to several of the inactivated COVID-19 shots distributed worldwide. The manufacturing process involves growing Vero cells in large bioreactors, infecting them with the target virus, harvesting the virus, and then purifying it through multiple steps designed to strip away cellular debris while preserving the viral material that trains your immune system.

Where Vero Cells Come From

The Vero cell line traces back to 1962, when researchers at Chiba University in Japan isolated kidney cells from an African green monkey (specifically, the species Chlorocebus sabaeus). Genomic analysis has confirmed the cells originated from a female animal and revealed they carry variations of an endogenous simian retrovirus, details that matter for quality control but pose no safety risk in finished vaccines because of the extensive purification involved.¹ The name “Vero” comes from a contraction of the Esperanto phrase meaning “truth,” chosen by the original researchers.

What makes these cells unusual is that they are “continuous” or “immortal,” meaning they keep dividing indefinitely in the laboratory rather than dying off after a set number of divisions the way normal cells do. That property was once a source of regulatory caution, since continuous cell lines were associated with cancer risk. But decades of safety data and improved purification methods have made Vero cells one of the most trusted platforms in the vaccine industry.

Why Vero Cells Are So Good at Growing Viruses

The single trait that makes Vero cells ideal for vaccine production is a genetic defect: they cannot produce interferon, the signaling molecule that healthy cells use to fight off viral infection.² In a normal cell, a virus enters and the cell raises the alarm by releasing interferon, which tells neighboring cells to ramp up their antiviral defenses. That alarm slows viral replication and makes it hard to collect large quantities of virus for vaccine manufacturing.

Vero cells skip that alarm entirely. When you infect them with a virus, it replicates freely and efficiently, producing high yields of viral material in a relatively short time. This is exactly what a vaccine manufacturer wants. The cells are also susceptible to a remarkably wide range of viruses, from rabies and poliovirus to influenza, dengue, and SARS-CoV-2, which is why the same cell platform keeps appearing across very different vaccine programs.

Which Vaccines Use Vero Cells

The list of Vero cell vaccines has grown steadily since the technology was first commercialized. The earliest large-scale applications were for rabies and polio. Vero cells are used to manufacture both inactivated polio vaccine and oral polio vaccine, as well as the purified Vero cell rabies vaccine (PVRV) that replaced older, less pure rabies shots in many countries.³

During the COVID-19 pandemic, Vero cells became globally visible through inactivated whole-virus vaccines such as Sinopharm’s BBIBP-CorV (marketed as “COVID-19 Vero Cell”), Sinovac’s CoronaVac, and Bharat Biotech’s Covaxin, all of which relied on growing SARS-CoV-2 in Vero cells and then chemically inactivating it.⁴ Beyond those, Vero cells are used in certain influenza vaccines, Japanese encephalitis vaccines, and experimental dengue and yellow fever candidates currently in development.⁵ The platform’s flexibility is a major reason it keeps being chosen for new projects.

Step One of Manufacturing: The Cell Bank

Every Vero cell vaccine starts with a carefully maintained cell bank. Manufacturers create a master cell bank, a frozen stock of Vero cells at a known, low passage number. A working cell bank is then derived from the master bank for day-to-day production. Both banks undergo rigorous quality testing established by the World Health Organization, including checks for identity, sterility, viability, mycoplasma contamination, retroviruses, tuberculosis bacteria, and other adventitious agents.⁶ This banking system ensures that every production run begins from a genetically consistent, well-characterized starting point.

The passage number, essentially a count of how many times the cells have been divided and regrown, is tracked carefully throughout this process for safety reasons discussed later in the article.

Growing Cells at Scale

Vero cells are naturally adherent, meaning they need a surface to attach to in order to grow. In a small laboratory, that surface might be the inside wall of a plastic flask. But for industrial-scale vaccine production, manufacturers use microcarriers, tiny beads (often made of cross-linked dextran) that float in liquid growth medium inside a bioreactor. The cells attach to these beads, and because the beads provide an enormous combined surface area, you can grow billions of cells in a single vessel.

This microcarrier approach has been in use since at least the early 1980s, when it was applied to inactivated poliovirus vaccine production.⁷ Modern bioreactors range from small vessels of a few liters for initial propagation to large stirred-tank systems of several thousand liters for full-scale production.⁸ Wave-type bioreactors, which rock gently to mix the contents, are commonly used for the early expansion stages, while stirred-tank reactors handle the larger volumes needed for commercial batches.

One concrete example of the yields this system achieves: researchers growing hepatitis A virus in Vero cells on Cytodex-I microcarriers inside a 7-liter bioreactor reported that cell density climbed from an initial seeding of 100,000 cells per milliliter to 14 million cells per milliliter over 28 days, producing about three times more viral antigen per cell than conventional static culture in flasks.⁹

Serum-Free Media and Why It Matters

Traditionally, Vero cells were grown in medium supplemented with fetal bovine serum, a nutrient-rich liquid derived from cattle blood. That works, but it introduces animal-derived proteins into the manufacturing process, which complicates purification and raises concerns about potential contaminants like bovine spongiform encephalopathy agents. The industry has therefore moved toward serum-free and animal-component-free media.

Multiple vaccine programs have successfully demonstrated production using serum-free conditions. A rabies vaccine produced in serum-free Vero cell culture achieved residual cellular DNA levels below about 23 picograms per dose, well under regulatory limits.¹⁰ Serum-free platforms have also been described for influenza vaccine candidates and chimeric virus vaccines, confirming the approach works across different virus types.¹¹¹² Eliminating serum simplifies the downstream purification steps considerably, since there are fewer unwanted proteins to remove from the final product.

Purifying the Vaccine

Once the virus has replicated to sufficient levels, the harvest fluid is a messy mixture: viral particles, fragments of dead Vero cells, residual DNA from those cells, host cell proteins, and whatever remains of the growth medium. The purification process, sometimes called downstream processing, strips all of that away while keeping the virus intact.

A typical sequence involves clarification (removing large cell debris), chromatography (selectively separating the virus from smaller impurities), ultrafiltration and diafiltration (concentrating the virus and exchanging it into a clean buffer solution), and sometimes nuclease digestion (using an enzyme to chop up residual DNA into fragments small enough to be washed away). In one well-documented example for a COVID-19 vaccine made in Vero cells, clarification alone reduced host cell protein content by roughly 30 percent without significantly reducing the viral content. A subsequent chromatography step removed almost all remaining host cell protein while leaving the virus largely untouched. By the end of the full process, host cell protein concentration was reduced about five-fold from the starting harvest, while the viral content was concentrated about 80-fold, indicating very efficient purification.¹³

Residual DNA is a particular focus of regulatory attention. For a Vero cell rabies vaccine, a combination of ultrafiltration, nuclease digestion, and gel filtration chromatography brought residual host cell DNA below 100 picograms per milliliter in the final product.¹⁴ Other published processes for rabies vaccine achieved both DNA levels under 100 picograms per dose and bovine serum protein levels under one part per million, while recovering more than 95 percent of the virus.¹⁵

Monitoring What Gets Left Behind

Regulators require manufacturers to measure exactly how much residual Vero cell material ends up in each dose of vaccine. Two key impurities are tracked: residual host cell DNA and residual host cell proteins. For DNA, the concern is theoretical, that DNA from a continuous cell line could, in principle, integrate into a recipient’s genome and cause problems. For host cell proteins, the concern is more practical, that leftover proteins could trigger unwanted immune reactions.

Sensitive assays have been developed specifically for Vero cell vaccines. One newer method for detecting host cell proteins in rabies vaccine achieved a detection limit of 0.011 micrograms per milliliter with recoveries in the range of 97 to 102 percent, providing regulators with confidence that contamination levels are accurately measured.¹⁶ Meanwhile, testing for adventitious viruses, accidental viral contaminants that could sneak into the production process, uses both cell culture-based assays and animal-based assays. In systematic evaluations, the cell culture tests detected all 16 test viruses, though some required special conditions, while the older animal-based tests detected only about half.¹⁷ This is one reason the field has been shifting toward more modern, cell-based and molecular detection methods.

The Passage Number Problem

The single biggest safety concern with Vero cells is not the cells themselves at the passage levels used for manufacturing, but what they become if you keep dividing them far beyond those levels. Studies going back to the 1980s have shown that Vero cells acquire tumorigenic potential, the ability to form tumors when injected into animals, as their passage number climbs. Cells at passage 232 and higher produced nodules in all nude mice tested in one early study.¹⁸

More detailed work confirmed that at the passage levels used for vaccine manufacturing, around passage 140, Vero cells are non-tumorigenic. Problems emerged only at much higher passages. Cells passaged beyond 200 produced tumors in roughly a third of adult nude mice and about two-thirds of newborn nude mice.¹⁹ Further research showed that it was high passage number itself, not culture conditions like the type of medium used, that drove the transformation. Low-passage Vero cells showed some abnormalities in certain laboratory tests but did not form tumors in animals.²⁰

This is precisely why the cell banking and passage tracking system exists. Regulatory agencies set strict limits on the passage number that can be used in production, and the purification steps described above remove residual cellular DNA that could theoretically carry tumorigenic genetic material. The combination of low-passage cells and thorough purification is what gives regulators confidence that Vero cell vaccines are safe.

Advantages Over Egg-Based Vaccines

Egg-based manufacturing, the traditional method for influenza vaccines in particular, requires millions of fertilized chicken eggs. Each egg is individually inoculated with virus, incubated, harvested, and discarded. The process works, but it has real limitations: it depends on a reliable supply of specific pathogen-free eggs, takes months to scale up, and can introduce egg-adapted mutations that reduce vaccine effectiveness. People with severe egg allergies may also need to avoid egg-derived vaccines, though in practice the amount of egg protein in modern flu shots is usually too small to cause reactions in most allergic individuals.

Cell culture-based production using Vero cells avoids these constraints. Vero cells can be thawed from a frozen bank and expanded to production scale in weeks rather than the months required for egg supply chains, offering shorter lead times and greater flexibility, a critical advantage during pandemics.²¹ The process also eliminates the egg allergy concern entirely and avoids the risk of egg-adapted viral changes.

For rabies vaccines, where Vero cell technology has been established the longest, head-to-head trials have shown that the purified Vero cell rabies vaccine produces antibody responses comparable to the older human diploid cell vaccine while causing fewer local and systemic reactions.²²²³ The Vero cell version is also substantially cheaper to produce, which has made it the vaccine of choice in tropical, rabies-endemic regions where the high cost of the diploid cell alternative previously limited access.

The Push Toward Suspension Culture

Even with microcarrier technology, growing adherent cells at industrial scale involves complications. The beads need careful handling, cells must be detached from them during harvest, and scaling up to very large bioreactors introduces engineering challenges around oxygen transfer and mixing. For years, researchers have been working on adapting Vero cells to grow in suspension, floating freely in liquid medium without needing any attachment surface. This would bring Vero cell manufacturing closer to the simpler processes used for cell lines that are naturally suspension-adapted.

Recent progress suggests this is becoming practical. One group adapted Vero cells to suspension growth in chemically defined medium, specifically to address the scalability limitations of microcarrier-based production for oncolytic measles virus, which requires very high viral doses per treatment.²⁴ Another research team developed a suspension Vero cell line and found it produced about 30 percent more poliovirus (depending on the serotype), 140 percent more respiratory syncytial virus, and 150 percent more yellow fever virus compared to the same cells grown in the traditional adherent format.²⁵ A separate study found that Vero cells adapted to suspension actually produced adenovirus type 5 better than adherent Vero cells did.²⁶

RNA sequencing of suspension-adapted cells has revealed that the genes involved in cell adhesion and matrix attachment are completely shut off, while signaling pathways related to growth factors show altered activity. Supplementing with fibroblast growth factor 2 boosted cell density by about 20 percent in one of these suspension lines.²⁵ If suspension Vero cells prove robust enough for commercial manufacturing, they could simplify the process substantially by eliminating the need for microcarrier beads and making it easier to harvest virus from the culture fluid without first detaching cells from a surface. That kind of process simplification matters because in a pandemic, weeks saved in manufacturing scale-up can translate directly into lives saved.