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Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine

Our take —

This was a successful phase 1 trial with few adverse events and robust immune responses, comparable to or even stronger than those of recovered COVID-19 patients. The NVX-CoV2723 recombinant nanoparticle vaccine by Novavax warrants further investigation in a phase 2 trial due to these promising results.

Preprint review

This expert summary page was originally written on August 21, 2020 to assess the preprint report of the NVX-CoV2723 vaccine candidate. The preprint report was later peer-reviewed and published in the NEJM, as linked above. We reviewed the updated article on September 14 and determined that it remained very similar to the preprint. Therefore, our assessment below remains up-to-date.

Study design

Randomized Controlled Trial

Study population and setting

This phase 1/2 trial took place in Melbourne, Australia and examined the safety and immunogenicity of the NVX-CoV2373 vaccine developed by Novavax. NVX-CoV2723 is a recombinant nanoparticle vaccine comprised of the SARS-CoV-2 spike protein, which binds to the human ACE2 receptor. 134 healthy males and females between the ages of 18 and 59 were randomized into five groups to test 5 and 25ug doses of the vaccine with and without Matrix-M1 saponin-based adjuvant. Participants received vaccine doses on day 0 and day 21 in alternating deltoids, and data collection ended on day 35 for analysis.

Summary of Main Findings

Reactogenicity to the vaccine was mild, and it was generally well-tolerated by most participants. The use of the M1 adjuvant increased reactogenicity, but symptoms reported were generally ≤ grade 1. Adverse events usually lasted for ≤ 2 days. Strong anti-spike IgG antibody responses were detected by day 21, and even more so by day 28 (after the second vaccination). Neutralizing antibodies followed a similar trend, with the adjuvant vaccine showing a strong correlation between neutralizing antibody titers and anti-spike IgG. Following the second vaccination, these levels exceeded those found in convalescent serum from patients hospitalized due to SARS-CoV-2. Finally, antigen specific CD4+ T-cells were generated and produced inflammatory cytokines upon spike protein stimulation.

Study Strengths

This study has several strengths, including the fact that it is an alternative vaccine strategy compared to other COVID-19 vaccine candidate front-runners. Multiple dose groups were employed, and the use of adjuvant showed promising results for dose-sparing and vaccine efficacy. Antibody titers as well as T-cell responses were measured in this trial, and metrics were comparable to those from convalescent serum from patients requiring medical care for SARS-CoV-2.

Limitations

This trial only focused on a short observation time for safety and immunogenicity data, but such is the nature of phase 1 trial design. The population studied in this trial had no Black participants, and few non-white participants in general. Therefore, this particular trial did not encompass some of the most vulnerable and hard-hit groups in the COVID-19 pandemic.

Value added

First results from phase 1/2 trial of the NVX-CoV2373 recombinant nanoparticle vaccine.

This review was posted on: 21 August 2020