This supplementary appendix provides additional information about the Phase 1–2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine (NVX-CoV2373). The study involved multiple institutions and sites, with key contributors listed. The trial included safety monitoring rules, RT-PCR testing methods, immunologic assay details, and descriptions of convalescent sera used for comparative analysis. Safety monitoring rules included pausing vaccinations if adverse events met specific criteria, such as grade 3 toxicity or specific laboratory abnormalities. RT-PCR testing was conducted using the TaqPath COVID-19 RT PCR combo kit. Immunologic assays included ELISA for IgG responses and microneutralization assays to measure neutralizing antibodies. Convalescent sera were collected from 32 patients with confirmed COVID-19 and tested using the same methods as the trial. Supplemental results showed that laboratory abnormalities of grade 2 or higher occurred in 10% of participants, primarily involving hemoglobin levels. No clinical manifestations were associated with these abnormalities. Unsolicited adverse events were investigated, but all were negative for SARS-CoV-2. The study also included detailed tables and figures, such as the Consort Flow Diagram, adverse event percentages, and geometric mean titers of IgG and neutralizing antibodies. The results showed strong immune responses, with participants demonstrating significant IgG and neutralizing antibody levels compared to convalescent sera. The study highlights the safety and immunogenicity of the NVX-CoV2373 vaccine.This supplementary appendix provides additional information about the Phase 1–2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine (NVX-CoV2373). The study involved multiple institutions and sites, with key contributors listed. The trial included safety monitoring rules, RT-PCR testing methods, immunologic assay details, and descriptions of convalescent sera used for comparative analysis. Safety monitoring rules included pausing vaccinations if adverse events met specific criteria, such as grade 3 toxicity or specific laboratory abnormalities. RT-PCR testing was conducted using the TaqPath COVID-19 RT PCR combo kit. Immunologic assays included ELISA for IgG responses and microneutralization assays to measure neutralizing antibodies. Convalescent sera were collected from 32 patients with confirmed COVID-19 and tested using the same methods as the trial. Supplemental results showed that laboratory abnormalities of grade 2 or higher occurred in 10% of participants, primarily involving hemoglobin levels. No clinical manifestations were associated with these abnormalities. Unsolicited adverse events were investigated, but all were negative for SARS-CoV-2. The study also included detailed tables and figures, such as the Consort Flow Diagram, adverse event percentages, and geometric mean titers of IgG and neutralizing antibodies. The results showed strong immune responses, with participants demonstrating significant IgG and neutralizing antibody levels compared to convalescent sera. The study highlights the safety and immunogenicity of the NVX-CoV2373 vaccine.