Are the First Two COVID Vaccines Still Relevant?
No, the original monovalent Pfizer-BioNTech and Moderna COVID-19 vaccines are no longer recommended as booster doses and have been replaced by updated formulations targeting current circulating variants. However, they remain acceptable for completing primary vaccination series in certain contexts, though updated 2024-2025 vaccines are strongly preferred for all doses when available.
Current Vaccination Strategy
The FDA removed emergency use authorizations for monovalent COVID-19 booster doses in September-October 2022, replacing them with bivalent formulations 1. The Advisory Committee on Immunization Practices (ACIP) now recommends that all persons aged ≥6 months receive the 2024-2025 COVID-19 vaccine formulation, regardless of prior vaccination history 1, 2.
Why Original Vaccines Were Superseded
The original monovalent vaccines demonstrated several critical limitations:
Decreased effectiveness against Omicron variants: Vaccine effectiveness (VE) against infection and COVID-19-associated hospitalization declined substantially during the Omicron-predominant period compared to the high effectiveness seen after vaccine introduction in late 2020 1.
Waning protection over time: Even with booster doses, VE against COVID-19-associated hospitalization waned over time, especially during BA.2/BA.2.12.1 and BA.4/BA.5 sublineage-predominant periods 1.
Immune evasion by variants: The Omicron variant, which emerged in November 2021, demonstrated increased immune evasion compared to earlier variants, creating a mismatch between the ancestral strain used in original vaccines and circulating viruses 1.
Current Recommendations by Vaccination Status
For Previously Vaccinated Individuals
All persons who previously received any COVID-19 vaccine (including original Pfizer-BioNTech or Moderna) should receive one dose of the 2024-2025 COVID-19 vaccine at least 8 weeks after their last dose 1, 2. The 2024-2025 vaccines are updated monovalent formulations specifically developed against current virus variants (Omicron JN.1-line, including JN.1 and KP.2) 2.
For Unvaccinated Individuals
Unvaccinated persons aged ≥12 years need only 1 dose of the 2024-2025 COVID-19 vaccine (Moderna, Pfizer-BioNTech, or Novavax) to be considered up to date 1. The exception is Novavax, which requires 2 doses for those who have never received any COVID-19 vaccine 1.
For Children Aged 6 Months to 4 Years
Children in this age group require an initial multidose vaccination series, needing more than 1 COVID-19 vaccine dose, including at least 1 dose of the 2024-2025 formulation 1.
Special Populations
Immunocompromised Individuals
Persons with moderate or severe immunocompromise should receive at least 1 dose of the 2024-2025 COVID-19 vaccine, with additional doses potentially recommended depending on vaccination history 1, 3. Unvaccinated immunocompromised persons aged ≥12 years should complete an initial 3-dose series of 2024-2025 mRNA vaccine or 2 doses of 2024-2025 Novavax 1.
After the initial 2024-2025 dose, immunocompromised individuals may receive 1 additional age-appropriate dose at least 2 months later 3.
Clinical Implications for Practice
When Original Vaccines May Still Be Used
While the original monovalent vaccines are no longer recommended for boosters, they may still be encountered in primary series completion scenarios. If an adult received a pediatric dose of original Moderna vaccine in error, they should receive a full adult dose of an approved 2024-2025 COVID-19 vaccine at least 8 weeks after the pediatric dose, and the error should be reported to VAERS 2.
Vaccine Interchangeability
The choice of vaccine manufacturer does not need to match prior vaccinations 2, 4. Individuals can choose from available 2024-2025 vaccine options (Moderna, Pfizer-BioNTech, or Novavax for those ≥12 years) regardless of which original vaccine they received 1, 2.
Timing Considerations
Persons who recently had a SARS-CoV-2 infection may consider delaying vaccination by 3 months from symptom onset or positive test result to allow their natural immune response to mature 2, 4, 3.
Common Pitfalls to Avoid
Do not use original monovalent vaccines as booster doses: The FDA removed EUAs for monovalent boosters, and ACIP repealed previous recommendations for their use 1.
Do not count pediatric doses as valid adult doses: If a vaccination error occurred, an additional age-appropriate dose must be administered 2.
Do not delay updated vaccination beyond recommended timeframes: This prolongs the period of suboptimal protection, particularly for high-risk individuals 2, 3.
Do not overlook immunocompromised status: These individuals require special vaccination considerations, including additional primary doses and potential extra booster doses 1, 4, 3.
Evidence Quality and Evolution
The transition from original to updated vaccines represents an evidence-based response to viral evolution. The original Pfizer-BioNTech and Moderna vaccines demonstrated 95% and 94.5% efficacy respectively against the ancestral strain 5, 6, 7, with excellent safety profiles 5, 8. However, the emergence of immune-evasive variants necessitated vaccine updates to maintain protection against severe disease, hospitalization, and death 1.
The 2024-2025 vaccines provide better protection than previous formulations because they are specifically designed against currently circulating variants 2, 3, making them the clear choice for all vaccination scenarios moving forward.