In the high-stakes game of hide and seek between viruses and vaccines, sometimes you need to update your search image.
Imagine your immune system as a highly trained security team equipped with photo IDs of known criminals. Now imagine a criminal shows up wearing an excellent disguise—your security might let them slip right through. This is essentially what's happening with mumps in certain parts of the world today.
For decades, we've had an effective vaccine against mumps, dramatically reducing cases of the once-common childhood illness. But viruses, like criminals, can change their appearances. In China, the most common mumps virus now circulating belongs to what scientists call genotype F, while the vaccine strain used in many areas belongs to genotype A1 5 . Though they're the same virus, their different "disguises" mean the protection from the current vaccine may not be as strong as it could be1 .
This concerning mismatch has prompted scientists to develop a new, highly attenuated vaccine candidate specifically tailored to match the circulating virus—a story of scientific ingenuity that represents the next chapter in our ongoing battle against infectious diseases.
If you're of a certain age, you might remember a classmate with comically swollen cheeks, a telltale sign of mumps. This classic symptom results from the virus's tendency to infect the parotid salivary glands, but mumps can be much more than an uncomfortable childhood rite of passage.
The disease can cause serious complications including pancreatitis, orchitis (inflamed testicles), deafness, aseptic meningitis, and encephalitis1 4 . Before vaccination became widespread, mumps was a leading cause of viral encephalitis in many developed countries4 .
The virus itself is a member of the Paramyxoviridae family, an enveloped particle containing a single strand of RNA approximately 15,384 nucleotides long4 . Its genome encodes several proteins, with the hemagglutinin-neuraminidase (HN) and fusion (F) proteins playing particularly important roles in entering host cells and triggering our immune response1 .
Scientists classify mumps viruses into 12 genotypes (A, B, C, D, F, G, H, I, J, K, L, and N) based on differences in a particular gene called SH1 . While there's only one serotype of mumps virus—meaning infection with one genotype should provide immunity against all others—the reality of cross-protection is more complicated.
Studies have revealed that cross-protection between genotypes may be limited1 . Serum antibodies from the Jeryl Lynn strain (genotype A) could neutralize other mumps genotypes, but the antibody levels against other strains were significantly lower than against itself1 . This helps explain why breakthrough mumps cases have occurred even in vaccinated populations1 2 .
| Genotype | Geographic Prevalence | Vaccine Strains | Notes |
|---|---|---|---|
| A | Global (vaccine strain) | Jeryl Lynn, RIT4385, S79, Wm84 | Used in most current vaccines |
| F | China | None (until recently) | Predominant circulating strain in China |
| G | United States, Europe | None | Caused recent outbreaks in vaccinated populations |
| Others (B, C, D, H, I, J, K, L, N) | Various regions | None | Circulate in specific geographic areas |
Creating a new vaccine involves walking a tightrope between two dangerous extremes: too weak, and it won't trigger adequate immunity; too strong, and it could cause the disease it's meant to prevent. The goal is what virologists call attenuation—weakening the virus just enough that it can't cause disease but can still stimulate a protective immune response.
Traditional mumps vaccines have been produced using primary chicken embryo cells, which presents several problems. This method consumes large numbers of chicken embryos (contrary to international 3R principles for ethical animal use) and carries potential risks like allergic reactions or contamination with avian retroviruses1 .
Chinese scientists therefore set out with an ambitious goal: develop an attenuated genotype F mumps strain using a more modern Vero cell line system, creating a vaccine candidate that would be safer to produce and more closely match the circulating virus1 .
The research, published in Frontiers in Immunology in 2025, followed a meticulous process to create and test their new vaccine candidates1 5 :
The journey began with collecting throat swabs from six suspected mumps patients during an outbreak in Changchun City, Jilin Province. From these samples, researchers isolated a wild-type genotype F mumps virus, designated "MuV-QBB"1 .
Unlike the wild virus, which isn't suitable for a vaccine, the researchers needed to adapt the virus to grow well in laboratory conditions. They passaged the virus multiple times in Vero cells, a standard mammalian cell line approved for vaccine production1 .
After adaptation, the researchers needed to isolate individual virus variants with desirable properties. Using a technique called plaque purification, they picked single virus plaques—clear areas where a single virus particle had infected and killed surrounding cells. Through this precise selection process, they identified two promising candidate strains: QBB-2BS-3.2 and QBB-2BS-9.31 .
The final and most crucial stage involved testing these candidates in animal models. The researchers immunized mice and measured the neutralizing antibody and cell-mediated immune responses. To assess potential neurological side effects (a concern with mumps vaccines), they conducted neurotoxicity studies in neonatal Lewis rats1 .
The experimental results revealed exciting findings that suggested the researchers had successfully created a promising vaccine candidate.
Both QBB-2BS-3.2 and QBB-2BS-9.3 elicited strong neutralizing antibody responses in immunized mice1 . This is particularly important because neutralizing antibodies are what primarily protect against future infections. The vaccine candidates also stimulated robust cell-mediated immune responses, which involve the T-cells that help eliminate virus-infected cells from the body1 .
| Vaccine Strain | Neutralizing Antibody Response | Cell-Mediated Immunity | Notes |
|---|---|---|---|
| QBB-2BS-3.2 | Strong | Robust | Genotype F candidate |
| QBB-2BS-9.3 | Strong | Robust | Genotype F candidate |
| S79 (Current vaccine) | Reference level | Reference level | Genotype A strain |
Perhaps even more importantly, the experimental strains showed minimal neurotoxicity in neonatal Lewis rats, a standard test for assessing potential neurological side effects of mumps vaccines1 . The neurotoxicity of both QBB-2BS-3.2 and QBB-2BS-9.3 was comparable to the S79 vaccine strain, which has a well-established safety profile1 .
This combination of strong immunogenicity and low neurotoxicity represents the ideal profile for a live attenuated vaccine candidate.
| Vaccine Strain | Neurotoxicity Level | Comparison to Reference |
|---|---|---|
| QBB-2BS-3.2 | Minimal | Comparable to S79 |
| QBB-2BS-9.3 | Minimal | Comparable to S79 |
| S79 (Reference) | Minimal | Baseline |
Behind this groundbreaking research lies an array of specialized tools and techniques that enabled the development and testing of the new vaccine candidates.
| Tool/Reagent | Function in Research | Example from Study |
|---|---|---|
| Vero Cells | Mammalian cell line for virus propagation and plaque assays | Used for adapting wild virus and quantifying virus potency1 |
| CCID₅₀ Assay | Measures virus infectivity by determining dilution that infects 50% of cell cultures | Used for virus titration and potency estimation1 7 |
| Plaque Assay | Alternative method to quantify infectious virus particles by counting clear zones in cell monolayer | Used for virus purification and quantification7 |
| Western Blotting | Detects specific viral proteins to confirm virus identity and composition | Used with anti-HN and anti-NP antibodies to detect viral proteins1 |
| Transmission Electron Microscopy (TEM) | Visualizes virus structure and morphology at high magnification | Used to confirm virus structure and integrity1 |
| Neutralization Assay | Measures levels of protective antibodies in immunized animals | Used to assess immunogenicity in mice1 |
| RT-PCR and Sequencing | Determines genetic sequence of virus and confirms genotype | Used for genetic characterization and phylogenetic analysis1 |
The development of a genotype F attenuated mumps vaccine candidate represents more than just a technical achievement—it exemplifies how vaccine science must continually adapt to changing pathogens.
While the current mumps vaccines have dramatically reduced disease incidence globally, the recent outbreaks in vaccinated populations highlight gaps in our protection that need addressing2 4 .
This research also demonstrates a shift toward more ethical and sustainable vaccine production methods by moving away from primary chicken embryo cells to cell line systems1 .
Additionally, other recent studies have confirmed the value of this approach, with a 2025 publication showing that another new mumps vaccine strain, MuV-365, also demonstrated strong immunogenicity and no potential neurotoxicity9 .
As the authors of the groundbreaking study concluded: "This study successfully developed two attenuated genotype F MuV candidate strains with favorable immunogenicity and safety profiles, laying a critical foundation for the development of genotype F mumps live attenuated vaccines"1 . While more testing is needed before these candidates might become widely available, they represent a promising step toward matching our vaccines to the viruses actually circulating in our communities.
In the endless dance between pathogens and scientific innovation, sometimes the most graceful step is knowing when it's time to learn some new moves.