Why Doesn't the CDC or WHO Offer More Seasonal Flu Candidate Vaccine Viruses (CVVs)?

The production of seasonal flu vaccines is a complex process that involves several key players and steps. The timeline and technological constraints mean that alternate approaches, such as offering more candidate vaccine viruses (CVVs), are not practical at present.

Understanding the Global Seasonal Flu Vaccine Production Process

The annual global seasonal flu vaccine production process commences in February when the World Health Organization (WHO) coordinates the Global Influenza Surveillance and Response System (GISRS). The GISRS comprises 143 WHO-designated National Influenza Centers (NICs) in 113 WHO Member States, as well as 6 WHO Influenza Collaborating Centers and several regulatory and reference labs.

These centers isolate the viruses currently circulating in their respective regions and submit them for analysis at Collaborating Centers (CCs), which conduct detailed antigenic analysis to determine the influenza A and B subtypes. The WHO then makes recommendations for the upcoming flu season's vaccine composition, taking into account the local epidemiological situation in each country/region.

This process ensures that vaccine manufacturers have a guide to develop and produce influenza vaccines tailored to the expected circulating strains. The Annual Influenza Vaccine Composition (AIVC) is recommended by the WHO in February/March for the northern hemisphere and September for the southern hemisphere. This allows for approximately 6-8 months to produce and approve vaccines, which is critical timing to ensure vaccine availability before the flu season.

The Major Bottleneck: Egg-Based Vaccines

The primary method used for growing seasonal flu vaccines involves the use of chicken eggs. This egg-based technique is hampered by several logistical challenges, including the time required for production.

Using eggs to grow flu vaccines takes at least 6 months, which is not only time-consuming but also creates other issues. The vaccine design cannot be easily altered mid-process, and there is a significant risk of egg shortages during avian flu epidemics. Additionally, the timing of the decision to include specific flu strains is made about 9 months before the start of the flu season, relying on an early snapshot of circulating strains that may change by the time the vaccine reaches the market.

The extended period required for growth means there is a greater chance for viral mutations to occur within the egg-based process. These mutations can lead to reduced vaccine efficacy, as the adapted strains may not match the circulating strains during the flu season. Studies, such as those by Raymond Donald D. et al., have highlighted the significance of such process-induced limitations.

Addressing the Challenges with Alternative Approaches

Efforts to develop more flexible and effective methods for producing seasonal flu vaccines have been ongoing. Alternative approaches include cell-based, recombinant protein-based, and plant-based techniques. However, these methods face significant challenges in terms of cost, time, and regulatory approval.

The cell-based approach has shown promise, but it has yet to gain widespread adoption due to the need for extensive clinical trials and the associated expenses. The recombinant and plant-based methods are also being tested, but they have not yet reached the same level of adoption as traditional egg-based vaccines.

A more ambitious goal is the development of universal flu vaccines that could offer broader protection against multiple strains of the influenza virus. However, this remains a significant scientific challenge, as researchers continue to work on understanding the specifics of what constitutes an effective immune response to the flu and how to elicit this response consistently.

Conclusion

While the egg-based approach remains the cornerstone of current seasonal flu vaccine production, the limitations and challenges associated with this method have spurred ongoing research and development of alternative techniques. The complexity and time required for these new approaches mean that offering more candidate vaccine viruses (CVVs) to enhance vaccine efficacy is not yet a practical solution.

Ultimately, the key to improving seasonal flu vaccination rates and overall effectiveness lies in continued innovation and the eventual breakthrough of more efficient and adaptable vaccine production methods.