Safety of the NVX-CoV2373 COVID-19 vaccine in randomized placebo-controlled clinical trials.

BACKGROUND: NVX-CoV2373 (Nuvaxovid™ or the Novavax COVID-19 Vaccine, Adjuvanted), the first protein-based COVID-19 vaccine, received emergency use authorization (EUA) as a primary series/booster and is available globally. NVX-CoV2373 primary series demonstrated efficacy rates of 89.7-90.4 % and an acceptable safety profile. This article summarizes safety in adult recipients (aged ≥ 18 years) of primary series NVX-CoV2373 in four randomized placebo-controlled trials. METHODS: All participants who received NVX-CoV2373 primary series or placebo (pre-crossover) were included according to actual received treatment. The safety period was from Day 0 (first vaccination) to unblinding/receipt of EUA-approved/crossover vaccine, end of each study (EOS), or last visit date/cutoff date minus 14 days. The analysis reviewed local and systemic solicited adverse events (AEs) within 7 days after NVX-CoV2373 or placebo; unsolicited AEs from after Dose 1 to 28 days after Dose 2; serious AEs (SAEs), deaths, AEs of special interest, and vaccine-related medically attended AEs from Day 0 through end of follow-up (incidence rate per 100 person-years). FINDINGS: Pooled data from 49,950 participants (NVX-CoV2373, n = 30,058; placebo, n = 19,892) were included. Solicited reactions after any dose were more frequent in NVX-CoV2373 recipients (local, 76 %/systemic, 70 %) than placebo recipients (local, 29 %/systemic, 47 %), and were mostly of mild-to-moderate severity. Grade 3+ reactions were infrequent, with greater frequency in NVX-CoV2373 recipients (local, 6.28 %/systemic, 11.36 %) than placebo recipients (local, 0.48 %/systemic, 3.58 %). SAEs and deaths occurred with similarly low frequency in NVX-CoV2373 (SAEs: 0.91 %, deaths: 0.07 %) and placebo recipients (SAEs: 1.0 %, deaths: 0.06 %). INTERPRETATION: To date, NVX-CoV2373 has displayed an acceptable safety profile in healthy adults. FUNDING: Supported by Novavax, Inc.

A Severe Acute Respiratory Syndrome Coronavirus 2 Anti-Spike Immunoglobulin G Assay: A Robust Method for Evaluation of Vaccine Immunogenicity Using an Established Correlate of Protection.

As the COVID-19 pandemic continues, variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge. Immunogenicity evaluation of vaccines and identification of correlates of protection for vaccine effectiveness is critical to aid the development of vaccines against emerging variants. Anti-recombinant spike (rS) protein immunoglobulin G (IgG) quantitation in the systemic circulation (serum/plasma) is shown to correlate with vaccine efficacy. Thus, an enzyme-linked immunosorbent assay (ELISA)-based binding assay to detect SARS-CoV-2 (ancestral and variant strains) anti-rS IgG in human serum samples was developed and validated. This assay successfully met acceptance criteria for inter/intra-assay precision, specificity, selectivity, linearity, lower/upper limits of quantitation, matrix effects, and assay robustness. The analyte in serum was stable for up to 8 freeze/thaw cycles and 2 years in -80 °C storage. Similar results were observed for the Beta, Delta, and Omicron BA.1/BA.5/XBB.1.5 variant-adapted assays. Anti-rS IgG assay results correlated significantly with neutralization and receptor binding inhibition assays. In addition, usage of international reference standards allows data extrapolation to WHO international units (BAU/mL), facilitating comparison of results with other IgG assays. This anti-rS IgG assay is a robust, high-throughput method to evaluate binding IgG responses to S protein in serum, enabling rapid development of effective vaccines against emerging COVID-19 variants.

Immunogenicity and safety of NVX-CoV2373 as a booster: A phase 3 randomized clinical trial in adults.

BACKGROUND: To combat the SARS-CoV-2 pandemic, multiple vaccines using different manufacturing platforms have been developed, including NVX-CoV2373 (an adjuvanted recombinant protein vaccine). As SARS-CoV-2 variants have emerged, some of which evade vaccine-induced immunity, introduction of vaccine booster doses has become critical. Employing different vaccine types for primary series vaccination and boosting could expand vaccine coverage and access. This study assessed whether NVX-CoV2373 would induce robust responses when used as a booster. METHODS: The 2019nCoV-307 study was a phase 3, randomized, observer-blinded trial evaluating immunogenicity and safety of NVX-CoV2373 in previously vaccinated adults aged 18-49 years in the United States (NCT05463068). Participants were randomized 1:1:1 to receive one intramuscular injection of NVX-CoV2373 from one of three different manufacturing lots. Immunogenicity was assessed by immunoglobulin G (IgG) and neutralizing antibodies (NAb). These responses were compared for the three lots, and for participants with primary series with or without a prior booster dose of the mRNA-1273, BNT162b2, Ad26.COV2.S, or NVX-CoV2373 COVID-19 vaccines. RESULTS: A total of 911 participants were randomized between July 11 and 13, 2022, with 905 being assessed for safety and 848 for immunogenicity. Immunogenicity of NVX-CoV2373 met prespecified equivalence criteria between lots, and the booster dose was well-tolerated. NVX-CoV2373 induced robust IgG and NAb responses when used as a first or later booster dose, regardless of primary series vaccine type. Seroconversion rates were also similar across previous vaccine types. Induced antibodies were strongly reactive, even to the immune-evasive Omicron BA.1 and BA.5 variants. CONCLUSIONS: NVX-CoV2373 showed consistent immunogenicity between lots, with no new safety signals identified. Use of NVX-CoV2373 as a booster dose (first or later) is supported.