Recent evidence demonstrates that individuals who have received two or three COVID-19 vaccines with booster shots should still obtain updated 2024-2025 vaccines to maintain optimal protection against circulating variants. Current public health guidance emphasizes that vaccination history does not exempt individuals from receiving updated formulations, as vaccine effectiveness wanes over time and new variants continue to emerge with enhanced immune evasion capabilities.
Current Vaccination Recommendations for Previously Vaccinated Individuals
Universal Recommendation for Updated Vaccines
The Centers for Disease Control and Prevention (CDC) recommends that all persons aged 6 months and older receive the 2024-2025 COVID-19 vaccine, explicitly including those who have previously received COVID-19 vaccines. This recommendation applies regardless of previous vaccination status, reflecting the understanding that immunity from earlier vaccines diminishes over time and may be less effective against newer circulating variants. The Advisory Committee on Immunization Practices (ACIP) made this recommendation on June 27, 2024, targeting currently circulating strains of SARS-CoV-2 to provide additional protection against severe COVID-19.
The updated 2024-2025 vaccines represent a significant advancement in targeting current variants. The Moderna and Pfizer-BioNTech vaccines are based on the KP.2 strain, while the Novavax vaccine targets the JN.1 strain. These formulations were specifically designed to address the Omicron JN.1 lineage strains that have been widely circulating in the United States since winter 2023-2024. The World Health Organization’s Technical Advisory Group on COVID-19 Vaccine Composition continues to support monovalent JN.1 or KP.2 vaccines as appropriate vaccine antigens, with monovalent LP.8.1 serving as a suitable alternative.
Age-Specific and Risk-Based Recommendations
Different vaccination schedules apply based on age and immunocompromise status. For individuals aged 12-64 years without immunocompromising conditions, one dose of the 2024-2025 vaccine is sufficient to maintain up-to-date status, regardless of previous vaccination history. This streamlined approach recognizes that most healthy adults in this age group achieve adequate protection with a single updated dose.
Adults aged 65 years and older face enhanced recommendations due to their increased risk of severe COVID-19 outcomes. This population should receive two doses of any 2024-2025 COVID-19 vaccine administered 6 months apart, with a minimum interval of 2 months allowed for flexibility around typical COVID-19 surges, travel, and healthcare visits. The recommendation for dual dosing in older adults reflects data showing that this population experiences more rapid waning of vaccine-induced immunity and faces higher risks of hospitalization and death from COVID-19.
Individuals with moderate or severe immunocompromise represent the highest-risk category and require the most comprehensive vaccination strategy. These individuals should receive at least two doses of the 2024-2025 vaccine, with the possibility of additional doses based on shared clinical decision-making. The immunocompromised population includes those with active treatment for malignancy, hematologic malignancies, solid organ transplant recipients taking immunosuppressive therapy, individuals who have received chimeric antigen receptor T-cell therapy, recent hematopoietic cell transplant recipients, those with moderate or severe primary immunodeficiency, advanced or untreated HIV infection, or those taking certain immunosuppressive medications.
Vaccine Effectiveness and Protection Against Current Variants
Real-World Effectiveness Data
Recent effectiveness studies demonstrate that the 2024-2025 vaccines provide meaningful protection against current circulating variants. Among adults aged 18 years and older, vaccine effectiveness against COVID-19-associated emergency department or urgent care visits reached 33% during the first 7-119 days after vaccination. For immunocompetent adults aged 65 years and older, effectiveness against COVID-19-associated hospitalization was 45-46% across two different CDC networks during the same timeframe. Notably, adults aged 65 years and older with immunocompromising conditions still achieved 40% vaccine effectiveness against hospitalization, demonstrating that even high-risk populations benefit from updated vaccination.
These effectiveness rates, while appearing modest compared to initial COVID-19 vaccine trials, represent significant public health benefits when applied across large populations. The protection afforded by updated vaccines becomes particularly important given the continued circulation of SARS-CoV-2 variants with enhanced transmissibility and immune evasion capabilities. Studies in specialized populations further support the value of updated vaccination. Among Medicare beneficiaries with end-stage renal disease receiving dialysis, updated 2023-2024 vaccines demonstrated effectiveness of 47% against medically attended COVID-19 and 49% against hospitalization among those without additional immunocompromising conditions.
Protection Against Post-COVID Conditions
Updated vaccination provides benefits beyond preventing acute illness, including reduction in post-COVID conditions (long COVID). A comprehensive systematic review examining 78 observational studies found that two vaccine doses administered before infection reduce the odds of developing post-COVID conditions with moderate confidence, showing a pooled odds ratio of 0.69. Furthermore, booster doses may provide additional protection compared to primary series alone, with a pooled odds ratio of 0.85 for developing post-COVID conditions. For individuals who already have post-COVID conditions, vaccination appears safe and may reduce the odds of symptom persistence, with a pooled odds ratio of 0.73.
Regulatory and Policy Considerations
Evolving Approval Standards
The regulatory landscape for COVID-19 vaccines is undergoing significant changes that may affect future recommendations. The Food and Drug Administration has outlined new regulatory guidance for future COVID-19 vaccine boosters, implementing stricter approval standards for healthy Americans. Under these new guidelines, the agency will require clinical trials demonstrating safety and effectiveness before approving updated vaccines for healthy adults and children, representing a departure from previous practices that relied primarily on immunogenicity data.
These evolving standards reflect a more nuanced approach to vaccine approval based on risk stratification. For high-risk populations, including adults aged 65 years and older and individuals with immunocompromising conditions, the FDA will continue to accept immunogenicity data as sufficient evidence for approval. However, for healthy children and adults, randomized, placebo-controlled clinical outcome data will be required[11]. This policy shift acknowledges questions about the optimal frequency of booster vaccination in lower-risk populations while maintaining robust protection for those at greatest risk of severe outcomes.
International Perspective
The World Health Organization continues to emphasize the importance of COVID-19 vaccination as a public health countermeasure. WHO guidance states that vaccination should not be delayed in anticipation of access to vaccines with updated composition, reflecting the principle that timely protection with available vaccines outweighs potential benefits of waiting for future formulations[6]. This perspective aligns with the understanding that SARS-CoV-2 continues to undergo sustained evolution, making periodic updates to vaccine composition necessary to maintain effectiveness against circulating variants.
Special Population Considerations
Immunocompromised Individuals
Immunocompromised individuals require particular attention regarding updated vaccination due to their heightened vulnerability to severe COVID-19 outcomes and potentially reduced vaccine responses. Current recommendations specify that individuals aged 6 months and older with moderate or severe immunocompromise may receive additional doses of 2024-2025 COVID-19 vaccine beyond the standard recommendations, based on shared clinical decision-making[5]. This approach recognizes the heterogeneity within immunocompromised populations and allows for individualized strategies based on specific clinical circumstances.
Research in kidney transplant recipients during the Omicron era provides valuable insights into vaccination effectiveness in immunocompromised populations. Among kidney transplant recipients, 94.4% had received three or more vaccine doses, yet 8.1% still experienced moderate to critical COVID-19. Protective factors included receiving a vaccine booster within the past year, with an adjusted odds ratio of 0.414 for moderate to critical disease. These findings underscore the importance of maintaining current vaccination status in immunocompromised individuals.
Pediatric Populations
Children represent a unique consideration in updated COVID-19 vaccination strategies. For children aged 6 months through 4 years, vaccination schedules depend on previous vaccination history, with unvaccinated children requiring 2 doses of Moderna or 3 doses of Pfizer-BioNTech vaccines. Children aged 5-11 years require one dose of the 2024-2025 vaccine regardless of previous vaccination history. Evidence regarding vaccination effectiveness in preventing post-COVID conditions in children shows less robust protection compared to adults, with vaccination potentially not reducing odds of post-COVID conditions in children 18 years and younger.
Conclusion
Current evidence strongly supports the recommendation that individuals with previous COVID-19 vaccination, including multiple doses and boosters, should receive updated 2024-2025 vaccines. The rationale for continued vaccination includes waning immunity from previous doses, evolution of SARS-CoV-2 variants with enhanced immune evasion capabilities, and demonstrated effectiveness of updated vaccines against current circulating strains. While regulatory approaches may become more stringent for future vaccine updates, current recommendations emphasize the continued importance of vaccination in preventing severe COVID-19 outcomes, particularly among older adults and immunocompromised individuals. The decision to receive updated vaccines should be informed by individual risk factors, with healthcare providers playing a crucial role in guiding vaccination decisions for high-risk populations through shared clinical decision-making processes.
