REACTOGENICITY OF NUVAXOVID AND OTHER COMMERCIALIZED COVID-19 VACCINES: A SYSTEMATIC REVIEW OF RANDOMIZED CONTROLLED TRIALS
Author(s)
Alice Sanderson, MPhil1, Jose Luis Bartelt Hofer, PhD2, Manuela Gschwend, PhD3, Paul Miller, MSc1, Katie Reddish, BSc1, Joe W.E. Moss, PhD1, Neil Hansell, BSc1, Clotilde El Guerche-Séblain, PhD4, Charalampos Valmas, PhD4, Rachael McCool, BsC1.
1York Health Economics Consortium, York, United Kingdom, 2Global Director HE&OR Vaccines, Sanofi Vaccines, Lyon, France, 3Novavax, Gaithersburg, MD, USA, 4Sanofi, Lyon, France.
1York Health Economics Consortium, York, United Kingdom, 2Global Director HE&OR Vaccines, Sanofi Vaccines, Lyon, France, 3Novavax, Gaithersburg, MD, USA, 4Sanofi, Lyon, France.
OBJECTIVES: Nuvaxovid protein-based COVID-19 vaccine has demonstrated comparable efficacy to mRNA vaccines with evidence of reduced reactogenicity; however, granular, systematic evidence remains limited. This systematic literature review (SLR) presents clinical evidence on the reactogenicity profile of commercialized COVID-19 vaccines from randomized controlled trials (RCTs).
METHODS: A SLR (PROSPERO: CRD420251084936) searching across five databases, two clinical trial registers, and six HTA/regulatory agency webpages was conducted in July 2025, with a supplementary MEDLINE search in September 2025. RCTs of currently commercialized mRNA or protein-based COVID-19 vaccines in adults were included. Extracted data included trial and patient characteristics, and post-vaccination solicited adverse events (AEs), stratified by severity (grades 1-4), AE site (local or systemic) and prior immune status (primary vs booster doses).
RESULTS: Out of 6,245 screened records, 34 RCTs (17 placebo-controlled; 17 head-to-head trials) were eligible. Vaccines identified were Nuvaxovid (NVX-CoV2373 and NVX-CoV2601), BNT162b2, mRNA-1273, mRNA-1283, ARCT-154, ARCT-2301, PHH-1V and PHH-1V81. Across RCTs, Nuvaxovid had the largest number of randomized participants (n=30,953), followed by BNT162b2 (n=25,502), mRNA-1273 and mRNA-1283 (n=17,343). Patient characteristics were comparable for gender distribution and mean age ranges (≈30-70 years), except those targeting special groups (e.g. the elderly). Geographic location varied substantially, resulting in diverse ethnic representations (predominantly Caucasian [44%] and Asian [29%]), while presence of chronic conditions differed markedly, from ≤10% in some adult placebo-controlled trials to ≥90% in the elderly. The median, unadjusted incidence of overall solicited AEs for mRNA vs Nuvaxovid arms was 69.2% vs 48.9% for systemic, and 86.1% vs 63.1% for local AEs.
CONCLUSIONS: Descriptive SLR data support favourable reactogenicity profile for Nuvaxovid relative to mRNA vaccines. These heterogeneous trial data establish the foundational framework for an ongoing network meta-analysis that isolates and compares relative reactogenicity profiles across different severity grades, AE site and prior immune status.
METHODS: A SLR (PROSPERO: CRD420251084936) searching across five databases, two clinical trial registers, and six HTA/regulatory agency webpages was conducted in July 2025, with a supplementary MEDLINE search in September 2025. RCTs of currently commercialized mRNA or protein-based COVID-19 vaccines in adults were included. Extracted data included trial and patient characteristics, and post-vaccination solicited adverse events (AEs), stratified by severity (grades 1-4), AE site (local or systemic) and prior immune status (primary vs booster doses).
RESULTS: Out of 6,245 screened records, 34 RCTs (17 placebo-controlled; 17 head-to-head trials) were eligible. Vaccines identified were Nuvaxovid (NVX-CoV2373 and NVX-CoV2601), BNT162b2, mRNA-1273, mRNA-1283, ARCT-154, ARCT-2301, PHH-1V and PHH-1V81. Across RCTs, Nuvaxovid had the largest number of randomized participants (n=30,953), followed by BNT162b2 (n=25,502), mRNA-1273 and mRNA-1283 (n=17,343). Patient characteristics were comparable for gender distribution and mean age ranges (≈30-70 years), except those targeting special groups (e.g. the elderly). Geographic location varied substantially, resulting in diverse ethnic representations (predominantly Caucasian [44%] and Asian [29%]), while presence of chronic conditions differed markedly, from ≤10% in some adult placebo-controlled trials to ≥90% in the elderly. The median, unadjusted incidence of overall solicited AEs for mRNA vs Nuvaxovid arms was 69.2% vs 48.9% for systemic, and 86.1% vs 63.1% for local AEs.
CONCLUSIONS: Descriptive SLR data support favourable reactogenicity profile for Nuvaxovid relative to mRNA vaccines. These heterogeneous trial data establish the foundational framework for an ongoing network meta-analysis that isolates and compares relative reactogenicity profiles across different severity grades, AE site and prior immune status.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
CO139
Topic
Clinical Outcomes, Epidemiology & Public Health
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Vaccines