Is the Moderna (mRNA-1273) vaccine more effective than the Novavax (NVX-CoV2373) vaccine in terms of coverage, duration of protection, and prevention of hospitalization due to COVID-19?

COVID-19 Vaccine Comparison: Moderna vs Novavax

Based on current evidence, both Moderna (mRNA-1273) and Novavax (NVX-CoV2373) demonstrate high effectiveness against COVID-19, but Moderna shows superior real-world effectiveness against infection (98.1% vs 65.7-89%) and has more extensive data supporting its use across diverse populations and variants. 1

Initial Efficacy Against Original Strains

Moderna demonstrates higher initial efficacy:

• Moderna (mRNA-1273) showed 94.5% efficacy in preventing symptomatic COVID-19 in phase III trials 2
• After full vaccination, Moderna demonstrated 98.1% effectiveness against SARS-CoV-2 infection in real-world settings 1
• Novavax (NVX-CoV2373) showed 89% efficacy against pre-Delta strains initially, declining slightly to 87% at 90 days 3

The mRNA platform used by Moderna delivers genetic instructions resulting in temporary expression of the SARS-CoV-2 spike protein, triggering both humoral and cellular immune responses 4. This mechanism has proven highly effective across multiple real-world evaluations 5, 6.

Duration of Protection

Both vaccines show evidence of waning, but with different patterns:

Moderna/mRNA Vaccines:

• Sustained 86% effectiveness against COVID-19-associated hospitalization at 2-12 weeks post-second dose 5
• Maintained 84% effectiveness at 13-24 weeks with no significant decline (p = 0.854) 5
• Protection against infection wanes over time, particularly during Omicron periods, but a third monovalent booster dose restores protection 7
• At 6 months post-vaccination, some decline in infection protection was observed 8

Novavax:

• Against pre-Delta strains: minimal waning through 90 days (89% to 87%, p = 0.93) 3
• Against Delta strain: moderate waning from 88% at 40 days to 82% at 120 days to 77% at 180 days (p < 0.01) 3
• Sensitivity analyses showed Delta vaccine efficacy at 120 days ranged from 66% to 89% depending on surveillance data assumptions 3

Critical caveat: Moderna has established booster strategies with bivalent formulations targeting both original and Omicron BA.4/BA.5 variants 7, 4, while Novavax booster data is more limited.

Prevention of Hospitalization

Moderna demonstrates exceptional protection against severe outcomes:

• 97.2% effectiveness against COVID-19-related hospitalization in fully vaccinated populations 1
• 97.4% effectiveness against ICU admission 1
• 99.0% effectiveness against death 1
• Among adults ≥65 years, 94% effectiveness against hospitalization after full vaccination 6
• Effectiveness against hospitalization remained 86% at 2-12 weeks and 84% at 13-24 weeks post-second dose 5

Novavax hospitalization data is less extensively documented in the provided evidence, though the high efficacy against symptomatic disease (87-89%) suggests substantial protection against severe outcomes 3.

Variant Coverage

Moderna has more comprehensive variant data:

• Effective against Alpha, Beta, Gamma, and Delta variants 8
• Bivalent boosters specifically developed for Omicron BA.4/BA.5 sublineages 7, 4
• During Delta predominance, effectiveness was maintained at high levels 5
• Reduced effectiveness against Omicron infection, but bivalent boosters restore protection 7

Novavax variant data:

• 88% initial efficacy against Delta strain 3
• Some experts suggest protein subunit-based vaccines like Novavax may have better safety profiles for patients with rheumatologic or autoimmune conditions 2

Special Populations

Both vaccines are recommended for high-risk groups, but Moderna has more extensive real-world data:

• Cancer patients: Moderna showed 83% efficacy in solid tumors and 72% in hematological malignancies 2
• Immunocompromised patients: A third dose of Moderna significantly increased anti-RBD antibody levels and T-cell counts in transplant recipients 2
• Pregnant women: mRNA vaccines (including Moderna) are recommended as benefits outweigh risks 2
• Chronic liver disease patients: mRNA vaccines like Moderna are specifically recommended by CDC 2

Current Recommendations

The Advisory Committee on Immunization Practices (ACIP) recommends:

• All persons aged ≥5 years receive a bivalent mRNA COVID-19 vaccine booster dose 7
• Booster should be administered at least 2 months after completion of primary series 7
• For immunocompromised patients (including cancer patients), booster shots within 3 months are recommended 2

Important consideration: Novavax may be preferred for patients with contraindications to mRNA vaccines or those with concerns about mRNA technology, and potentially for patients with autoimmune conditions 2.

Safety Profile

Both vaccines demonstrate excellent safety:

• Moderna: Anaphylaxis 2.5-4.7 cases per million doses; myocarditis 3.5 cases per million doses 8
• Serious adverse events are rare for both platforms 2, 8
• The benefits of COVID-19 vaccination outweigh the risks for both vaccines 8

Bottom line: While both vaccines are highly effective, Moderna demonstrates superior real-world effectiveness data, more extensive variant coverage including Omicron-specific boosters, better-documented durability against hospitalization, and established protocols for immunocompromised populations. Novavax remains an excellent alternative, particularly for those preferring traditional protein-based vaccine platforms or with specific contraindications to mRNA vaccines.