Covovax (NVX-CoV2373) / Novavax, Takeda, Serum Institute of India - LARVOL DELTA

The platform trial in COVID-19 priming and BOOsting (PICOBOO): The reactogenicity of nine licensed COVID-19 vaccines delivered in immunocompetent adults. (PubMed, Vaccine) - "Reactogenicity events were common but rarely severe. Although reactogenicity appeared less frequent following Nvx than mRNA vaccines within strata, the trial was not powered for between-vaccine comparisons and findings should be interpreted descriptively."

Journal • Fatigue • Infectious Disease • Musculoskeletal Pain • Novel Coronavirus Disease • Pain

Real-world effectiveness and safety of protein-based and mRNA COVID-19 vaccines (BEEHIVE trial). (PubMed, Vaccine) - "This is one of the earliest real-world trials evaluating the VE of the 2023-2024 COVID-19 vaccines (XBB.1.5). These results suggest that both protein-based and mRNA vaccines are well-tolerated and significantly reduce the risk of symptomatic SARS-CoV-2 infections."

Journal • Real-world evidence • Cardiovascular • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

Comparative analysis of non-clinical and clinical safety assessment of COVID 19 vaccines. (PubMed, Regul Toxicol Pharmacol) - "Five authorized vaccines were included in the analysis: tozinameran (Comirnaty®), elasomeran (Spikevax®), ChAdOx1-S (Vaxzevria®), Ad26.COV2-S (Jcovden®), and the SARS-CoV-2-S protein with Matrix-M (Nuvaxovid®). These rare events were not predicted by non-clinical studies as expected. While non-clinical studies currently meet regulatory safety requirements, their predictive capacity could be enhanced by integrating a reactogenicity scoring system, harmonizing biomarker monitoring, and adding targeted parameters based on clinical evidence."

Journal • Cardiovascular • Hematological Disorders • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • Thrombocytopenia

Safety and Immunogenicity of NVX-CoV2705 (clinicaltrialsregister.eu) - P3 | N=660 | Sponsor: Sanofi Vaccines US Inc.

New P3 trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Immunogenicity and safety of a SARS-CoV-2 recombinant vaccine S-268024 booster vaccination versus NVX-CoV2373: Interim results from a phase 3, multicenter, randomized, observer-blind, active-controlled study. (PubMed, Vaccine) - "Interim analyses established noninferiority and superiority of S-268024 to NVX-CoV2373 in immunogenicity, with an acceptable safety profile."

Journal • P3 data • P3 data: top line • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Safety and immunogenicity of a COVID-19-Influenza Combination nanoparticle vaccine (CIC) containing SARS-CoV-2 recombinant spike and quadrivalent influenza hemagglutinin with Matrix-M® adjuvant: A phase 1/2 clinical trial. (PubMed, Hum Vaccin Immunother) - "The CIC vaccine group had similar incidence of solicited and unsolicited AEs as the qNIV and NVX-CoV2373 reference groups. Severe unsolicited AEs only occurred in the CIC group but were infrequent and not considered related to the study vaccine. Overall, CIC formulations displayed reference-comparable safety and immunogenicity and provided data for statistical modeling analyses to optimize influenza hemagglutinin and SARS-CoV-2 rS antigen concentrations for use in phase 2 clinical trials investigating CIC."

Clinical • Journal • P1/2 data • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases

Short-Term Safety and Adverse Event Risk Profiles for SARS-CoV-2 Booster Vaccine Doses in Australian Adults: A Survey Study. (PubMed, Med J Aust) - "The results of this study confirm the short-term safety and low impact on daily living of SARS-CoV-2 booster vaccine administration to Australian adults."

Adverse events • Journal • Fatigue • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

PICOBOO: A randomised trial to evaluate the immune response of COVID-19 vaccines in adults and adolescents (ANZCTR) - P4 | N=1325 | Active, not recruiting | Sponsor: The Kids Research Institute Australia | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Novel Coronavirus Disease

SOLVE-01: An Experimental Medicine Multicenter Trial to Evaluate the Safety and Immunogenicity of Experimental Versus Authorized SARS-CoV-2 Vaccine Candidates as a Booster Dose in Healthy Participants Previously Vaccinated With Authorized mRNA SARS-CoV-2 Vaccines. (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: ANRS, Emerging Infectious Diseases | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine and Influenza Combination Vaccine (clinicaltrials.gov) - P3 | N=9320 | Completed | Sponsor: Novavax | Trial completion date: Sep 2026 ➔ Feb 2026 | Trial primary completion date: Jul 2026 ➔ Dec 2025 | Active, not recruiting ➔ Completed

Trial completion • Trial completion date • Trial primary completion date • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases

SAFETY AND IMMUNOGENICITY OF TWO DOSES OF THE NOVAVAX PROTEIN-BASED VACCINE IN CHILDREN AGED 6–23 MONTHS: A PHASE 2/3 RANDOMIZED, PLACEBO-CONTROLLED TRIAL COHORT 3 (ESPID 2026) - P2/3 | "Our study aimed to evaluate the safety, tolerability, and immunogenicity of the Novavax ancestral COVID-19 vaccine (NVX-CoV2373) in 6–23-month-old children (Cohort 3) through a Phase 2/3 age de-escalation study...The GMT in the vaccine group was 4926 (95% CI: 4470–5429) at Day 35 via the MN assay, representing a GMFR ratio of 147.9 from baseline, with responses non-inferior to those in adults 18–<26 in the pivotal efficacy study. Conclusions/Learning Points In a study of 6–23-month-old children, a two-dose NVX-CoV2373 regimen showed an acceptable safety profile and elicited immunogenic responses by prespecified assays, with no unexpected safety signals, supporting continued pediatric clinical evaluation."

Clinical • P2/3 data • Infectious Disease • Novel Coronavirus Disease

SHIELD: Impact of Reactogenicity of the 2024-2025 COVID-19 Vaccines on Health Care Workers and First Responders in the United States (clinicaltrials.gov) - P4 | N=660 | Completed | Sponsor: Novavax | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Validation of a Mucosal IgA Assay for SARS-CoV-2. (PubMed, Microorganisms) - "After validation using Omicron XBB.1.5 rS protein, cross-reactivity was demonstrated with the SARS-CoV-2 variant JN.1. This validated IgA assay can be a valuable tool to assess mucosal IgA levels in SARS-CoV-2 clinical trials."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

SOLVE-01: An Experimental Medicine Multicenter Trial to Evaluate the Safety and Immunogenicity of Experimental Versus Authorized SARS-CoV-2 Vaccine Candidates as a Booster Dose in Healthy Participants Previously Vaccinated With Authorized mRNA SARS-CoV-2 Vaccines. (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: ANRS, Emerging Infectious Diseases

New P1 trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Study to Evaluate Safety and Immunogenicity of COVID-19 Vaccine in Children 6 Months to < 12 Years (clinicaltrials.gov) - P2/3 | N=3600 | Completed | Sponsor: Novavax | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

COVID-19: Efficacy and Safety of NVX-CoV2705 (clinicaltrials.gov) - P4 | N=6500 | Active, not recruiting | Sponsor: Novavax | Not yet recruiting ➔ Active, not recruiting | Trial completion date: Jul 2026 ➔ Dec 2026 | Trial primary completion date: Jan 2026 ➔ Dec 2026

Enrollment closed • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Humoral Immune Correlates Analysis of Four Vaccines Against SARS-CoV-2 in Rhesus Macaques. (PubMed, Res Sq) - "We assessed correlates of protection (COP) in a vaccine trial of 126 Rhesus macaques randomized to placebo or one of four vaccines (mRNA-1273 [Moderna], Ad26.COV2.S [Janssen], NVX-CoV2373 [Novavax], and CoV2 preS dTM+AS03 [Sanofi]) at varying doses and challenged with SARS-CoV-2 (USA-WA1/2020 strain)...Further, the observed viral load for animals receiving each vaccine showed good agreement to their predicted values modelled only using data from animals receiving the other three vaccines (agreement coefficients between 0.25-0.59). These analyses suggest that neutralizing titers and antibody binding levels are correlates of protection that predict reduction in viral load across these four different vaccines."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

NVX-CoV2372, monovalent mRNA and bivalent mRNA vaccines elicit broadly cross-reactive antibodies against emerging SARS-CoV-2 variants. (PubMed, Hum Vaccin Immunother) - "Randomized clinical trials comparing the breadth and long-term persistence of immunity between different COVID-19 vaccine types and between ancestral and Omicron-targeted vaccines are limited. Improved neutralizing antibody responses against diverse SARS-CoV-2 variants by the ancestral or variant vaccine highlight the immunological benefits of COVID-19 vaccine boosters regardless of the latest variant-based vaccine. Further studies to determine if different vaccine combinations translate to differing protection against infection remain necessary."

Clinical • Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

mRNA and Protein Subunit COVID-19 Vaccine Reactogenicity and Their Relationship to Productivity for Healthcare Workers and First Responders. (PubMed, Open Forum Infect Dis) - P4 | "Fewer reactogenicity symptoms following COVID-19 vaccination suggest use of the 2024-2025 adjuvanted protein-based NVX vaccine as an immunization option with a lower impact on daily life. These findings may inform policymakers, clinicians, and hospital systems regarding vaccine tolerability, which may influence HCW and FR behavior regarding COVID-19 vaccines."

Journal • Infectious Disease • Novel Coronavirus Disease

Effect of time-of-day vaccination on the antibody response to mRNA and protein COVID-19 vaccine in adults. (PubMed, Vaccine) - "We explored if time-of-day vaccination influences antibody responses to a fourth dose of mRNA (Moderna bivalent vaccine; mRNA-1273.214/mRNA-1273.222) or protein (Novavax; NVX-CoV-2373) COVID-19 vaccine as part of a randomised controlled trial (RCT) in Melbourne, Australia. Time-of-day vaccination had no effect on the response to Novavax, regardless of sex. Larger randomised trials are needed to confirm these findings to optimise vaccine timing strategies."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Immunogenicity and efficacy over 12 months following a fourth dose of a bivalent mRNA or protein-based COVID-19 vaccine: A randomised controlled trial in Australia. (PubMed, J Infect) - "While the bivalent Moderna vaccine induced higher immune responses than the Ancestral Novavax vaccine as a fourth dose, both vaccines appeared to provide comparable protection against SARS-CoV-2 Omicron variants over 12-months."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IFNG

Safety of Matrix-M-adjuvanted COVID-19, seasonal influenza, combination influenza-COVID-19, and malaria vaccines: a review of the evidence. (PubMed, Expert Rev Vaccines) - "Two authorized Matrix-M - adjuvanted vaccines, NUVAXOVID (COVID-19) and R21/Matrix-M (Plasmodium falciparum malaria), have been administered to >10 million people worldwide. Active-comparator clinical trials and post-marketing studies demonstrate favorable reactogenicity profiles of Matrix-M - adjuvanted vaccines compared with licensed vaccines for the same diseases, particularly, lower reactogenicity rates post - NUVAXOVID versus mRNA COVID-19 vaccination. Research is ongoing to better characterize Matrix-M immune-stimulating mechanisms, continue technology improvements, and identify new applications to enhance vaccines and therapeutics."

Journal • Review • Infectious Disease • Influenza • Malaria • Novel Coronavirus Disease • Respiratory Diseases

COVID-19 Reactogenicity (clinicaltrials.gov) - P4 | N=1000 | Active, not recruiting | Sponsor: Marcel Curlin | Trial completion date: Jun 2028 ➔ Jun 2026 | Trial primary completion date: Apr 2027 ➔ Jun 2026 | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Impact of prior SARS-CoV-2 acquisition on binding and neutralizing antibody responses following COVID-19 vaccination: A cross-protocol analysis of individual-level data from six phase 3 clinical trials. (PubMed, Vaccine) - "In SARS-CoV-2-naïve individuals, a two-dose vaccine regimen is needed to provide antibody levels correlated with protection against disease caused by the cognate virus strain. In contrast, in individuals with prior SARS-CoV-2 acquisition, a single dose of any of the tested vaccines/platforms (mRNA/protein/vector) provides comparably high antibody levels."

Journal • P3 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Evaluating Safety and Immune Response of Janssen, Moderna, Pfizer/BNT, and Novavax COVID-19 Vaccines for Same and Mixed Boosters in Adolescents and Adults Aged 12-64 With and Without HIV in Kenya, DRC, and Rwanda (clinicaltrials.gov) - P2 | N=1919 | Completed | Sponsor: Victoria Biomedical Research Institute

New P2 trial • Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD4