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ABSTRACT
Introduction
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in significant morbidity and mortality worldwide. As SARS-CoV-2 moves into endemic status, vaccination remains a key element in protecting the health of individuals, societies, and economies worldwide.
Areas covered
NVX-CoV2373 (Novavax, Gaithersburg, MD) is a recombinant protein vaccine composed of SARS-CoV-2 spike trimer nanoparticles formulated with saponin-based Matrix-M™ adjuvant (Novavax, Gaithersburg, MD). NVX-CoV2373 is authorized for emergency use in adults and adolescents aged ≥12 years in the United States and numerous other countries.
Expert opinion
In clinical trials, NVX-CoV2373 showed tolerable reactogenicity and favorable safety profiles characterized by mostly mild-to-moderate adverse events of short duration and by low rates of severe and serious adverse events comparable to those seen with placebo. The two-dose primary vaccination series resulted in robust increases in anti-spike protein immunoglobulin G, neutralizing antibody titers, and cellular immune responses. NVX-CoV2373 vaccination was associated with complete protection against severe disease and a high (90%) rate of protection against symptomatic disease in adults, including symptomatic disease caused by SARS-CoV-2 variants. Additionally, the NVX-CoV2373 adjuvanted recombinant protein platform offers a means to address issues of COVID-19 vaccination hesitancy and global vaccine equity.
Article highlights
The aim of this Vaccine Profile is to characterize the NVX-CoV2373 adjuvanted, recombinant protein vaccine and summarize available clinical and immunogenicity data.
NVX-CoV2373 is an authorized COVID-19 recombinant protein vaccine composed of the full-length SARS-CoV-2 Wuhan-Hu-1 spike protein as self-assembling nanoparticles combined with the novel adjuvant, Matrix-M.
Matrix-M is a saponin-based adjuvant that promotes a broad-based, robust humoral and cellular immune response and offers potential advantages over other adjuvants.
The traditional recombinant protein-based platform and standard refrigeration storage conditions of NVX-CoV2373 offer a means to address global vaccine equity and provide an alternative for those who may be vaccine hesitant toward newer technologies.
Reactogenicity and safety data gathered from Phase II and Phase III trials in which NVX-CoV2373 was given as a primary series and as a first or second homologous booster reveal well-tolerated reactogenicity and an overall favorable safety profile including a low incidence of severe and serious adverse events comparable to placebo in adolescents and young and older adults.
In two large Phase III clinical trials, NVX-CoV2373 provided 100% protection against severe COVID-19 disease and approximately 90% vaccine efficacy against symptomatic disease, including symptomatic disease caused by then-circulating variants (mainly alpha and beta), in adults across various subpopulations, age ranges, and in those with comorbidities for high-risk disease; a post hoc analysis of data from the US Phase III trial also revealed 100% protection against hospitalization.
NVX-CoV2373 was associated with a vaccine efficacy of 80% in adolescents 12-17 years old during a period of delta variant predominance.
A two-dose primary series with NVX-CoV2373 elicits a robust increase in anti-spike IgG and neutralizing antibody titers regardless of SARS-CoV-2 serostatus, age, HIV status, or co-administration with an age-appropriate seasonal influenza vaccine.
After a first or second homologous booster with NVX-CoV2373, antibody levels significantly increase to levels considerably higher than the post-primary series levels, and the magnitude of difference between the ancestral strain and VOCs, including Omicron BA.1, BA.2, and BA.4/BA.5, is reduced with each booster dose, suggestive of potential broad protection against newly-evolving variants.
The well-characterized recombinant protein vaccine technology platform employed for the manufacture of NVX-CoV2373 plus Matrix-M adjuvant affords ongoing flexibility and timeliness to respond to evolving SARS-CoV-2 immune escape variants to meet the needs of future boosters.
Abbreviation List
| ACE2 | = | angiotensin-converting enzyme 2 |
| AE | = | adverse event |
| AESI | = | adverse event of special interest |
| ARF | = | acute rheumatic fever |
| CI | = | confidence interval |
| COVID-19 | = | coronavirus disease 2019 |
| ECG | = | electrocardiogram |
| EU | = | enzyme-linked immunosorbent assay units |
| EUA | = | emergency use authorization |
| EudraCT | = | European Union Drug Regulating Authorities Clinical Trials |
| FDA | = | U.S. Food and Drug Administration |
| hACE2 | = | human angiotensin-converting enzyme 2 |
| IC >99% | = | inhibitory concentration > 99% |
| IgG | = | immunoglobulin G |
| MAAE | = | medically attended adverse events |
| MI | = | myocardial infarction |
| MRI | = | magnetic resonance imaging |
| PACTR | = | Pan African Clinical Trials Registry |
| PLWH | = | people living with HIV |
| rS | = | recombinant spike |
| SAE | = | serious adverse events |
| SARS-CoV-2 | = | severe acute respiratory syndrome coronavirus 2 |
| Sf9 | = | Spodoptera frugiperda |
| TEAE | = | treatment-emergent adverse events |
| UK | = | United Kingdom |
| US | = | United States |
| VOC | = | variant of concern |
| VOI | = | variant of interest |
| WHO | = | World Health Organization |
Acknowledgments
Medical writing support for the development of this review, under the direction of the authors, was provided by Tiffany DeSimone, PhD, CMPP; Carol Duffy, PhD, and Kelly Cameron, PhD, CMPP, of Ashfield MedComms (US), an Inizio company, which was funded by Novavax, Inc. The authors would like to thank Anthony Marchese, PhD, of Novavax, Inc. for his support and expertise updating the manuscript after peer review. Research support was provided by Sharon Glass of Novavax, Inc.
Declaration of interest
R M. Mallory, S Galbiati, K Alves, S Toback, G Áñez, L M. Dunkle, A McGarry, W Woo, V Shinde, C Bennett, E Underwood, K Smith, L Fries, I Cho, G M. Glenn, and G Chau are or were all employees or contractors of Novavax and as such received compensation for their work, and might be shareholders of Novavax, Inc. S A. Madhi reports receiving grant support, paid to his institution, from Bill and Melinda Gates Foundation, Novavax, Pfizer, GlaxoSmithKline, and MinervaX, and receiving honoraria from Sanofi for lecture (unrelated to the current study). P T. Heath reports receiving grant support, paid to his institution, from Novavax, Pfizer, Moderna, Valneva, Astra Zeneca, and MinervaX. K L. Kotloff reports receiving grant support, paid to her institution, from NIAID for her work on the vaccine trial. C L. Gay reports receiving grant support, paid to her institution, from NIAID for her work on the vaccine trial. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript apart from those disclosed.
Information resources
Further information on NVX-CoV2373 clinical trials can be found at the study registration sites, including:
ClinicalTrials.gov: https://clinicaltrials.gov/
European Union Drug Regulating Authorities Clinical Trials Database (EudraCT): https://eudract.ema.europa.eu/
Pan African Clinical Trials Registry (PACTR): https://pactr.samrc.ac.za/
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/14760584.2023.2218913.
Author contributions
Eddie Underwood developed the first draft of the manuscript. All other authors reviewed/revised the manuscript.