Influenza viruses constantly evolve, posing a recurring public health challenge. Flu vaccines are a primary defense, and their development is a continuous process of scientific advancement. Innovations have improved how these vaccines are produced, their composition, and the methods used to predict target strains each year, aiming for broader and more effective protection.
Conventional Vaccine Production
Historically, the most common method for producing flu vaccines has involved using fertilized chicken eggs. Candidate vaccine viruses are injected into millions of eggs, where they replicate within the egg’s fluid over several days.
The fluid containing the viruses is harvested from the eggs. For inactivated vaccines, the viruses are inactivated and purified to isolate the viral antigens. This traditional egg-based approach has been a reliable method for over 70 years, forming the backbone of flu vaccine supply.
Advanced Manufacturing Techniques
Newer manufacturing techniques have emerged, moving beyond the traditional egg-based approach. Cell-based vaccine production utilizes cultured mammalian cells instead of chicken eggs to grow influenza viruses. This method offers advantages such as faster start-up times, reduced reliance on chicken egg supply, and avoids mutations that can occur when viruses adapt to eggs, which might improve the match between the vaccine virus and circulating wild flu strains.
Recombinant vaccine technology represents another significant advancement, as it does not require an influenza virus or chicken eggs in its production. It isolates the genetic instructions for a specific viral protein, typically hemagglutinin (HA), which triggers an immune response. This HA gene is combined with a baculovirus and introduced into insect cells. These cells produce large quantities of the HA protein, which is then purified and formulated into the vaccine. This approach allows for rapid production and ensures precise, laboratory-made antigens without the live virus.
Enhanced Vaccine Compositions
Beyond manufacturing, vaccine compositions have improved, leading to broader and stronger protection. Quadrivalent vaccines protect against four different flu strains. For many years, flu vaccines were trivalent, targeting two influenza A and one influenza B virus. The addition of a second influenza B strain in quadrivalent vaccines provides wider coverage, particularly beneficial when both B lineages circulate. Most flu vaccines are now quadrivalent, offering enhanced protection.
Adjuvants are substances added to some vaccines to boost the immune response, helping the body create a stronger reaction to vaccine antigens. For instance, the MF59 adjuvant enhances immune responses, especially in older adults who often have a diminished immune response. High-dose vaccines are also available for people aged 65 and older. These vaccines, such as Fluzone High-Dose, contain four times the antigen amount of standard vaccines, aiming to elicit a stronger protective immune response in this population. Studies show high-dose and adjuvanted flu vaccines offer better protection for seniors against flu symptoms and hospitalization.
Smarter Strain Selection
The effectiveness of flu vaccines depends on accurately predicting which influenza strains will circulate. This prediction process has advanced through global collaboration and sophisticated technologies. The World Health Organization (WHO) coordinates the Global Influenza Surveillance and Response System (GISRS), a global network of laboratories. GISRS monitors influenza virus spread and evolution, collecting and analyzing thousands of flu virus samples year-round.
Improved genomic sequencing allows rapid and detailed analysis of viral genetic material, helping scientists understand how flu viruses are changing. This data, combined with global surveillance, informs the WHO’s twice-annual meetings where experts recommend flu strains for upcoming vaccine compositions. Computational modeling and machine learning algorithms are increasingly used to predict viral evolution and predominant strains. These models contribute to more accurate strain selection and more effective annual flu vaccines.