Changes in Vaccine Ingredients Over the Past 50 Years
The most significant change in vaccine ingredients over the past 50 years has been the substantial reduction or elimination of thimerosal (a mercury-containing preservative) from most vaccines, particularly those administered to children and infants.
Thimerosal Use and Reduction
Thimerosal, a mercury-containing compound (49.55% mercury by weight), has been used as a preservative in vaccines since the 1930s to prevent bacterial contamination, particularly in multi-dose vials 1, 2.
In 1999, the U.S. Public Health Service and other organizations recommended efforts to reduce or eliminate thimerosal in vaccines to decrease total mercury exposure, particularly among infants, despite no scientific evidence indicating that thimerosal in vaccines led to serious adverse events 1.
Since mid-2001, vaccines routinely recommended for infants in the United States have been manufactured either without thimerosal or with only trace amounts (<1 mcg mercury/dose) 1.
The shift from thimerosal-containing vaccines to thimerosal-free or reduced-thimerosal vaccines represents a dramatic change in vaccine composition over the past 50 years 1.
Specific Changes in Thimerosal Content
50 years ago (1970s): Thimerosal was commonly used in multi-dose vaccine vials at concentrations of approximately 25 mcg mercury per 0.5-mL dose 1, 2.
Current vaccines (2000s-present):
- Multi-dose inactivated influenza vaccines still contain 25 mcg mercury/0.5-mL dose 1.
- Single-dose syringes of inactivated influenza vaccines contain only trace amounts of thimerosal (<1 mcg mercury/0.5-mL dose) 1.
- Live attenuated influenza vaccine (LAIV) contains no thimerosal 1.
- Most childhood vaccines now contain either no thimerosal or only trace amounts 1.
By 2004,27 of 29 vaccine products under CDC contract did not contain thimerosal as a preservative, compared to only 15 of 28 products in 1999 1.
Other Vaccine Components and Manufacturing Changes
Basic composition: Both past and present vaccines typically contain antigens (parts of pathogens that stimulate immunity), which for influenza vaccines include hemagglutinins of virus strains likely to circulate in the upcoming season 1.
Growth medium: Both past and present influenza vaccines are initially grown in embryonated hens' eggs, which may result in limited amounts of residual egg protein in the final product 1.
Inactivation process: For inactivated vaccines, manufacturers may use different compounds to inactivate viruses and add antibiotics to prevent bacterial contamination. These processes have varied by manufacturer over time 1.
Formulations: Modern vaccines include more purified subvirion and surface antigen preparations compared to earlier vaccines 1.
Safety Considerations
Despite concerns about thimerosal, studies have not found harmful effects from the quantities of mercury, aluminum, formaldehyde, human serum albumin, antibiotics, and yeast proteins in vaccines 3.
The reduction of thimerosal in vaccines was undertaken as a precautionary measure to decrease total mercury exposure, not because of demonstrated harm 1.
Recent research has raised questions about thimerosal's cytotoxicity at certain concentrations, with one 2023 study suggesting it may be more toxic to human and animal cells than to bacterial and fungal cells 4.
Some studies have suggested potential associations between thimerosal exposure and neurodevelopmental outcomes, though these remain controversial and have not led to changes in official recommendations 5.
Even in vaccines marketed as "thimerosal-free," trace amounts may still be detected, though at levels substantially lower than established safety limits (e.g., 10 ppb in one study of Infanrix hexa) 6.
Practical Implications
The shift away from thimerosal-containing vaccines represents a significant change in vaccine formulation over the past 50 years, driven by precautionary principles rather than evidence of harm 1.
For patients concerned about thimerosal, single-dose formulations without preservatives or with only trace amounts are now widely available for most vaccines 1.
Despite changes in preservatives and manufacturing processes, the fundamental mechanism of vaccines—stimulating immunity through exposure to pathogen components—remains unchanged from 50 years ago 1.