Sarah Bennett
The influenza virus poses a serious public health problem, and vaccination is the most effective public health intervention against it. Most flu shots are produced from viruses grown in chicken eggs containing an embryo. This method is cost-effective, but it has limitations. For instance, the avian cells in chicken eggs are slightly different from human cells, which can lead to mutations in the virus that reduce the effectiveness of the vaccine. Additionally, the long growth phase in chicken eggs can cause the immune system to produce different antibodies than originally intended. These challenges have led to the development of alternative methods for producing flu vaccines, such as cell culture-based manufacturing, which offers faster and more stable production.
| Characteristics | Values |
|---|---|
| Type of vaccine | Influenza |
| Type of eggs | Chicken eggs containing an embryo |
| Part of the egg used | Allantois |
| Advantages | Cost-effective, fast, flexible |
| Disadvantages | Mutations can occur, less effective, long lead time, possibility of contamination, variability in yield, risk of mutation during the long growth phase |
| Alternative | Cell-based vaccines |
| Comparison | Cell-based vaccines are more expensive, but faster and more stable in production |
| Example of cell-based vaccines | Flucelvax, Optaflu |
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What You'll Learn
- Influenza vaccines are cheaper to produce in chicken eggs
- Chicken egg vaccines may be less effective due to mutations
- Avian cells are different from human cells, which can affect antibodies
- Cell-based vaccines are faster and more stable to produce
- Chicken egg vaccines can induce an antibody response against an egg-associated glycan
Influenza vaccines are cheaper to produce in chicken eggs
Influenza vaccines are generally made from inactivated flu viruses so that the vaccine itself won't make a person sick. These inactivated viruses can still trigger the immune system to produce antibodies to fight the virus. In the past, scientists discovered that large quantities of the flu virus could be grown in the allantoic fluid surrounding a chick embryo. This method of growing viruses in chicken eggs was pioneered by Sir Frank Macfarlane Burnet in 1936 and has been improved upon since then.
Today, most flu vaccines are still made in chicken eggs containing an embryo. This is because it is a cost-effective way to grow influenza viruses. For example, according to the CDC, an egg-based flu vaccine from Sanofi costs $16.94 per dose, while an equivalent egg-free vaccine costs $22.77 per dose.
However, there are some limitations to producing influenza vaccines in chicken eggs. Mutations can occur in influenza viruses grown in avian cells, leading to vaccines that are less effective because they are aimed at a slightly different version of the virus than the one circulating in the population. This is because avian cells are slightly different from human cells, particularly in the molecules that coat their surfaces. This makes it more difficult for human viruses to recognise and attach to avian cells. Sometimes, human flu viruses adapt or mutate to better grab the avian host cell receptors. These adaptations can occur in the hemagglutinin protein, which is the antigen that vaccines are designed to raise antibodies against. As a result, flu viruses that develop mutations in their surface proteins during vaccine manufacture may no longer match the ones circulating in the population, and therefore the vaccines may not protect people as well.
Despite these limitations, some argue that these mutations do not cause enough of a drop in vaccine effectiveness to justify abandoning egg-based vaccines, and more studies are needed. Furthermore, vaccines produced in cell culture may also have limitations, and their safety, tolerability, efficacy, and effectiveness are still being studied.
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Chicken egg vaccines may be less effective due to mutations
Chicken eggs have been used for decades as a cost-effective way to grow viruses for vaccines. However, recent evidence has emerged that the efficacy of flu shots may be affected by the process of growing viruses in chicken eggs.
The manufacturing process of the vaccine may also contribute to a low effectiveness against certain strains of the influenza virus by generating mutations in hemagglutinin induced by egg culture that affect its antigenicity. Genetic comparisons of hemagglutinin sequences of several egg-grown viruses have revealed that substitutions in the amino acid sequence of hemagglutinin alter their antigenic properties. This can lead to a decrease in vaccine effectiveness.
While some experts believe that these mutations cause a significant drop in vaccine effectiveness, others argue that more studies are needed to justify abandoning egg-based vaccines. Egg-based vaccines are still extremely useful, even in years where their effectiveness is in the mid-range of 40-50%. Additionally, egg-based vaccines are cheaper than egg-free ones, which can be an important consideration for vaccine manufacturers.
Overall, while chicken egg vaccines have been a valuable tool in the fight against influenza, there is growing evidence that mutations occurring during the egg-based vaccine production process may lead to reduced vaccine effectiveness. Further research and consideration of alternative vaccine production methods are needed to optimize vaccine effectiveness and protect public health.
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Avian cells are different from human cells, which can affect antibodies
Avian cells are different from human cells in several ways, including their immune response regulation and the types of cells involved. Birds have lymphoid tissues, B cells, T cells, cytokines, and chemokines like many other animals, but there are some key differences. For example, the avian immune system is divided into two types: innate and adaptive immunity. The innate immune system includes physical and chemical barriers, blood proteins, and phagocytic cells, while the adaptive immune system involves the production of antibodies by B cells.
In birds, the central organ for B cell development is the Bursa of Fabricius, which is located in the gut. The bursa is responsible for the primary site of B cell lymphopoeisis, and avian B cell development has unique properties compared to human or mouse models. For example, early studies on antibody responses to the flu found that antibodies were binding to a wide range of viruses, not just the flu virus. It was eventually discovered that the antibodies were responding to something in the biological material the viruses were grown in - specifically, chicken eggs. This finding highlights a difference in how avian and human cells can affect antibodies.
Another difference between avian and human cells is the absence of the protein tristetraprolin (TTP) in birds. TTP plays a crucial anti-inflammatory role in other animals by regulating TNFα. The absence of TTP in birds leads to a different immune response regulation compared to mammals, reptiles, and amphibians. Additionally, avian T cells have some unique features, including a new lineage of cytoplasmic CD3+ lymphoid cells (TCR0 cells) and a T cell sublineage that expresses a different receptor isotype (TCR3).
The differences between avian and human cells have implications for vaccine development. For example, the influenza vaccine has traditionally been grown in embryonated chicken eggs, but this method has limitations. The abundance of avian-type receptors in the chorioallantoid membrane favors the selection of variants that increase binding to avian-type receptors and reduce binding to human-type receptors, reducing the vaccine's effectiveness. Producing vaccines in cell culture, rather than chicken eggs, allows for a faster and more flexible response to potential pandemic threats and may improve the vaccine's effectiveness.
Furthermore, vaccines grown in eggs have been found to induce an antibody response against an egg-associated glycan called N-acetyllactosamine (LacNAc). While LacNAcs are common glycans in humans, the specific sulfur modification found in eggs is not expressed in humans. As a result, humans can produce antibodies against this sulfur-modified glycan, which may impact the effectiveness of the vaccine. However, it is important to note that these antibodies do not bind to known egg allergens, and it is unclear if they affect vaccine effectiveness.
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Cell-based vaccines are faster and more stable to produce
Flu vaccines are traditionally produced using chicken eggs. However, the process has its limitations. For instance, the virus has to be able to infect the host cells, which is more challenging due to the difference in surface receptors between avian and human cells. This can lead to mutations in the virus, which may reduce the effectiveness of the vaccine.
Cell-based vaccines, on the other hand, are produced in mammalian, avian, or insect tissue culture. Madin-Darby Canine Kidney (MDCK) cells are commonly used, but other cell lines such as monkey cell lines pMK and Vero, and human cell lines HEK 293, MRC 5, Per.C6, PMK, and WI-38 are also utilized. The use of these cells prevents the glycosylation introduced during the egg adaptation stage and the substitution of HA L194P in subtype H3N2.
Cell-based vaccines offer several advantages over traditional egg-based vaccines. Firstly, they are faster to produce. The immunogenicity and safety of influenza vaccines produced in cell culture have been extensively studied and are well-understood. Cell-based vaccines also allow for a more flexible response to potential pandemic threats. For example, during the COVID-19 pandemic, the speedy production and accessible distribution of vaccines were paramount for public health responses.
Additionally, cell-based vaccines are more stable. They avoid the issue of egg allergens and the risk of virus mutation during the long growth phase in chicken eggs, which can cause the immune system to produce an unintended antibody response. While the antibodies produced in response to these mutations do not appear to reduce the immune system's ability to produce anti-flu antibodies, it is not clear whether there is an impact on vaccine effectiveness.
Cell-based vaccines have been approved for use in various parts of the world. For instance, Flucelvax, a mammalian cell-based influenza vaccine, was approved in the United States in 2012, while Optaflu, a similar vaccine, was approved for use in the European Union in 2009. These vaccines have shown similar levels of vaccine efficacy and immunogenicity as traditional egg-based vaccines while offering the advantage of being suitable for people with egg allergies.
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Chicken egg vaccines can induce an antibody response against an egg-associated glycan
Chicken eggs have long been used as a cost-effective way to grow viruses for vaccines. However, vaccines grown in eggs can induce an antibody response against an egg-associated glycan. This means that vaccinated individuals produce an antibody response against a component in eggs that is unrelated to the virus. This discovery has raised questions about the effectiveness of vaccines grown in eggs and the potential need for alternative methods of vaccine production.
The antibody response against egg-associated glycans was discovered by researchers at the University of Chicago who spent years studying antibody responses against the flu. They found that the antibodies were binding not only to the flu virus but also to other viruses, which was an unusual pattern since antibodies typically target specific pathogens. Eventually, they realized that the antibodies were responding to something in the biological material in which the viruses were grown – specifically, the allantois of chicken eggs.
The antibodies target a sugar molecule called N-acetyllactosamine (LacNAc), which is a common glycan in humans. However, the LacNAc found in eggs has a sulfur modification that is not known to be expressed in humans. This sulfur-modified glycan can trigger the production of antibodies against it. While this antibody response is common after flu vaccination, it is unclear if it impacts vaccine effectiveness. Some evidence suggests that vaccines prepared by methods other than egg culture may be more effective, but the reasons are not fully understood.
The implications of the antibody response against egg-associated glycans are still unknown. While there is no evidence of negative health effects, it may be affecting immunity. More research is needed to determine the significance of these anti-egg antibodies and their impact on the flu-specific immune response.
In conclusion, chicken egg vaccines have been found to induce an antibody response against an egg-associated glycan, specifically a sulfur-modified form of LacNAc. This discovery highlights the potential limitations of egg-based vaccines and the need to explore alternative production methods to improve vaccine effectiveness.
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Frequently asked questions
Influenza vaccines are most commonly grown in chicken egg culture.
Chicken eggs are a cost-effective way to grow influenza viruses. They are also a well-characterized process with over thirty years of commercial scale application.
Chicken eggs are slightly different from human cells, which can make it difficult for human viruses to recognize and attach to the avian cells. This can lead to mutations in the virus, reducing the effectiveness of the vaccine.
Yes, vaccines can also be produced using mammalian cells, such as Madin-Darby canine kidney cells, monkey cell lines, and human cell lines. Cell-based vaccines may be more effective than egg-based vaccines as they do not carry the risk of viral mutation during the growth phase.
