What is the most effective COVID-19 (Coronavirus Disease 2019) vaccination currently available?

Best COVID-19 Vaccination Currently Available

The 2024-2025 formula COVID-19 vaccines (Moderna and Pfizer-BioNTech based on KP.2 strain, or Novavax based on JN.1 strain) are the best options currently available, with all persons aged ≥6 months recommended to receive at least one dose regardless of prior vaccination history. 1

Current Vaccine Formulations and FDA Authorization

The most recent vaccines have been specifically updated to match circulating variants:

• Moderna and Pfizer-BioNTech (2024-2025 Formula): FDA-approved for persons ≥12 years and authorized under EUA for children 6 months-11 years on August 22,2024, based on the KP.2 strain 1
• Novavax (2024-2025 Formula): FDA-authorized under EUA for persons ≥12 years on August 30,2024, based on the JN.1 strain 1

These updated formulations replaced the previous XBB.1-strain vaccines because SARS-CoV-2 has evolved, with Omicron JN.1 lineage strains (including JN.1 and KP.2) now widely circulating since winter 2023-2024. 1

Who Should Receive Vaccination

All persons aged ≥6 months should receive the 2024-2025 COVID-19 vaccine, as recommended by ACIP on June 27,2024. 1 This universal recommendation is based on:

• COVID-19 continues to cause thousands of hospitalizations and hundreds of deaths weekly in the United States 1
• Highest hospitalization rates occur in adults ≥75 years, followed by infants <6 months and adults 65-74 years 1
• In 2023,44,059 COVID-19 deaths occurred in persons ≥65 years 1
• Vaccine effectiveness wanes over time, necessitating updated formulations 1

Timing Considerations

For individuals with recent COVID-19 infection, postpone vaccination for 2-3 months after infection. 1, 2 This waiting period:

• Allows the immune system to recover 2
• May enhance vaccine response 2
• Reduces risk of adverse effects 2

For previously vaccinated individuals, administer the 2024-2025 vaccine ≥2 months after the last dose of any prior COVID-19 vaccine. 1, 3

mRNA Vaccines vs. Protein-Based Vaccines

While both mRNA vaccines (Moderna, Pfizer-BioNTech) and protein-based vaccines (Novavax) are authorized, the mRNA platforms have the most robust evidence for efficacy and safety:

• BNT162b2 (Pfizer-BioNTech): 97.84% vaccine efficacy against symptomatic COVID-19 (95% CI 44.25% to 99.92%) and 95.70% efficacy against severe/critical disease (95% CI 73.90% to 99.90%) 4
• mRNA-1273 (Moderna): 93.20% vaccine efficacy against symptomatic COVID-19 (95% CI 91.06% to 94.83%) and 98.20% efficacy against severe/critical disease (95% CI 92.80% to 99.60%) 4

High-certainty evidence demonstrates that both mRNA vaccines reduce all-cause mortality, severe COVID-19, and hospitalization. 4

Special Populations

Immunocompromised Individuals (Ages 6 months-11 years)

Complete at least a three-dose series with COVID-19 vaccine, each dose one month apart, with at least one dose being the 2024-2025 formula. 3 An additional dose may be administered ≥2 months following the last 2024-2025 formula dose at healthcare provider discretion. 3

Older Adults (≥65 years)

Prioritize vaccination in this age group due to significantly elevated risk. 1, 2 The elderly face higher COVID-19-related hospitalization, ICU admission, and mortality due to comorbidities, poor nutrition, depressed immunity, and lower organ function. 2

Cancer Patients

Strongly recommend vaccination early in cancer treatment, even if it cannot be given within the ideal timeframe. 1 Five nonrandomized studies demonstrate vaccination reduces severe COVID-19 illness risk in cancer patients. 1 Vaccinated cancer patients with COVID-19 are significantly less likely to experience hospitalization or death within 30 days (odds ratio 0.44,95% CI 0.28 to 0.72). 1

For immunocompromised cancer patients, administer additional vaccine doses after a 2-month interval. 1

Pregnant and Breastfeeding Women

COVID-19 vaccine should be offered to pregnant women, with preferential administration for those at highest risk of severe infection. 1 Although pregnant women were excluded from initial trials, they are at higher risk of severe COVID-19-related illness. 1

Safety Profile

The most common adverse events are mild to moderate (grade 1 or 2), including injection site pain, fatigue, myalgia, headache, and fever. 1, 2

Serious adverse events (SAEs) show little or no difference compared to placebo for mRNA vaccines:

• mRNA-1273 (Moderna): RR 0.92 (95% CI 0.78 to 1.08) 4
• The likely absolute difference in SAEs is fewer than 5 per 1000 participants 4

Rare cardiac events (myocarditis, pericarditis) have been reported in postmarketing surveillance but remain uncommon. 3

Common Pitfalls to Avoid

• Do not delay vaccination indefinitely in immunocompromised patients awaiting "optimal" timing - vaccinate early in treatment even if immunosuppression cannot be fully reduced 1
• Do not withhold vaccination from pregnant women - the benefits outweigh theoretical risks, especially for those at high risk 1
• Do not assume prior infection provides adequate protection - vaccination after natural infection enhances immunity and provides more robust protection against variants 2
• Do not use outdated vaccine formulations - only the 2024-2025 formulas are currently authorized 1