Encouraging results from Phase I NovaVax SARS-CoV-2 nanoparticle vaccine trial

NVX-CoV2373, a recombinant nanoparticle vaccine developed by Novavax and manufactured at Emergent Biosolutions, was found to be well tolerated and immunogenic – inducing T-cell response and neutralization antibodies four-fold higher than the mean observed in hospitalized coronavirus disease (COVID-19) patients, shows a recent study available on the medRxiv* preprint server.

Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread around the globe and resulted in the COVID-19 pandemic. This brought the whole research community together in the ongoing quest for the safe and effective vaccine, with several promising candidates already on the horizon.

A new vaccine generation based on nanoparticles has excellent potential in avoiding the limitations of conventional or subunit vaccines. More specifically, the latest advances in bioengineering allow the design of nanoparticles by precisely controlling shape, size, functionality, and surface traits – leading in turn to improved antigen presentation and robust immunogenicity.

Furthermore, recent studies appraising a recombinant seasonal influenza hemagglutinin nanoparticle vaccine, adjuvanted with Matrix-M1, suggested that the combination of this adjuvant with nanoparticle vaccine is not only safe but could also induce robust functional antibody and T-cell responses in elderly individuals with or without comorbidities.

A similar approach was swiftly pursued against SARS-CoV-2 as well. The first-in-human, phase 1 clinical trial, led by Dr. Cheryl Keech from Novavax Inc. in Gaithersburg (United States), evaluated both the safety and immunogenicity of NVX-CoV2373 vaccine candidate (with or without Matrix-M1 adjuvant) at two phase 1 clinical units in Australia.

Trial design and assessment details

NVX-CoV2373 is a recombinant nanoparticle vaccine manufactured from the full-length, wild-type SARS-CoV-2 spike glycoprotein. It is coupled with a saponin-based Matrix-M adjuvant in order to enhance the immune response and produce high levels of neutralizing antibodies, which are pivotal in halting the infection.

In a nutshell, this was a randomized, placebo-controlled, observer-blinded, phase 1 clinical trial in 131 healthy adults aged 18 to 59. Trial vaccination consisted of two intramuscular injections, which were administered 21 days apart.

Primary outcomes were reactogenicity, safety profile, and IgG anti-spike protein response. Secondary outcomes included adverse events appraisal, wild-type virus-neutralizing antibody production, as well as T- cell response.

Since this was a phase 1 clinical trial, unsolicited adverse events were assessed diligently for causality (not related and related) and clinical severity (mild, moderate, and severe). Assessments also included adverse events of special interest (AESI) relevant to COVID-19 and possible immune-mediated medical conditions.

Well tolerated with adequate safety profile

The primary immunogenicity and safety analyses suggest that in healthy adult participants, the two-dose regimens of 5 and 25 micrograms of NVX-CoV2373/Matrix-M1 were not only well-tolerated but also induced the most robust immune responses. The latter consisted of high levels of neutralizing antibodies in close correlation with anti-spike IgG.

"Furthermore, neutralizing antibody responses following second vaccination was of the magnitude seen in convalescent serum from hospitalized COVID-19 patients and exceeded overall convalescent sera GMT by four-fold", accentuate study authors in their medRxiv paper.

And if we turn our eye to Matrix-M1 adjuvant, we can also see that its benefit was clear – considering the induction of functional antibodies, the magnitude of the antibody and T-cell response, as well as dose sparing. Furthermore, antigen-specific T cells were largely exhibited T helper 1 (Th1) phenotype.

In any case, the findings reveal a safety profile that is acceptable and comparable to previous studies utilizing comparable platform technologies. In the majority of study subjects, only mild reactogenicity was noted, and an adjuvanted vaccine slightly increased the intensity and frequency of such events.

Further considerations

"Taken together, the adjuvanted, recombinant, full-length spike protein nanoparticle vaccine is a promising candidate that warrants rapid advancement into efficacy studies," emphasize study authors.

Moreover, this study reveals the value of the second vaccine dose in the proposed two-dose regimen, as very high levels of antibodies, achieved warrant the logistics of a boosting visit. Another benefit is a liquid formulation of the vaccine that allows successful cold chain management with existing infrastructure.

Naturally, this trial is not without limitations – most notably, if we take into account the length of time of safety observations and measured immune responses. It is clear that safety in the face of exposure to viral infection and immune response durability for SARs-CoV-2 vaccines will be of substantial interest.

However, these early results are encouraging, and we can welcome another candidate in our growing armamentarium of vaccines against SARS-CoV-2. Further stages of clinical trials will show if NVX-CoV2373 will become viable as some other promising options.

In July 2020, Novavax were selected to participate in Operation Warp Speed (OWS), a U.S. government sponsored program that aims to begin delivering millions of doses of a safe, effective vaccine for COVID-19 in 2021, under which the company will receive funding of $1.6 billion. OWS funds the late-stage clinical studies necessary to determine the safety and efficacy of NVX-CoV2373, including a pivotal Phase 3 clinical trial with up to 30,000 subjects beginning in the fall of 2020.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Dr. Tomislav Meštrović

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university - University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.

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