• Vaccine Name: NVX-CoV2373
• Target Pathogen: SARS-CoV-2
• Target Disease: COVID-19
• Tradename: Covovax
• Manufacturer: Novavax
• Vaccine Ontology ID: VO_0005155
• CDC CVX code: 211
• CDC CVX description: SARS-COV-2 (COVID-19) vaccine, Subunit, recombinant spike protein-nanoparticle+Matrix-M1 Adjuvant, preservative free, 0.5mL per dose
• Type: Subunit vaccine
• Status: Clinical trial
• Host Species for Licensed Use: Human
• Antigen: SARS-CoV-2 spike (S) glycoprotein (Keech et al., 2020)
• Immunization Route: Intramuscular injection (i.m.)
• Description: A recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant. (Keech et al., 2020)

Mouse Response

• Vaccination Protocol: Groups of mice were immunized with a dose range (0.01 μg, 0.1 μg, 1 μg, and 10 μg) of NVX-CoV2373 with 5 μg Matrix-M adjuvant using a single priming dose or a prime/boost regimen spaced 14 days apart. (Tian et al., 2021)
• Immune Response: Animals immunized with a single priming dose of 0.1–10 μg NVX-CoV2373/Matrix-M had elevated anti-S IgG titers that were detected 21–28 days after a single immunization. Mice immunized with 10 μg NVX-CoV2373/Matrix-M induced antibodies that blocked hACE2 receptor binding to S-protein and virus neutralizing antibodies 21–28 days after a single priming dose. Animals immunized with the prime/boost regimen had significantly elevated anti-S IgG titers that were detected 7–16 days following the booster immunization across all dose levels. Animals immunized with 1 μg and 10 μg NVX-CoV2373/Matrix-M had similar high anti-S IgG titers following immunization (geometric mean titer, GMT = 139,000 and 84,000, respectively). Importantly, mice immunized with 0.1 μg, 1 μg, or 10 μg NVX-CoV/Matrix-M had significantly (p ≤ 0.00006) higher anti-S IgG titers compared to mice immunized with 10 μg NVX-CoV2373 without adjuvant. Immunization with two doses of NVX-CoV2373/Matrix-M elicited high titer antibodies that blocked hACE2 receptor binding to S-protein (IC50 = 218–1642) and neutralized the cytopathic effect (CPE) of SARS-CoV-2 on Vero E6 cells (100% blocking of CPE = 7680–20,000) across all dose levels. (Tian et al., 2021)
• Challenge Protocol: Mice were immunized with a single priming dose or a prime/boost regimen with NVX-CoV2373/Matrix-M as described above. Since mice do not support replication of WT SARS-CoV-2 virus, BALB/c mice were transduced with adenovirus encoding human ACE2 receptor (Ad/hACE2) which renders them permissive to infection with SARS-CoV-2 (refs. 21,22). At 4 days post transduction, mice were challenged with 105 plaque forming units (pfu)/mouse of SARS-CoV-2 (WA1 strain). Following challenge, mice were weighed daily and pulmonary histology and viral load were analyzed at 4 and 7 days post challenge. (Tian et al., 2021)
• Efficacy: At 4 days post infection (dpi), placebo-treated mice had an average of 104 SARS-CoV-2 pfu/lung, while the mice immunized with NVX-CoV2373 without Matrix-M had 103 pfu/lung and those with Matrix-M had limited to no detectable virus load. The NVX-CoV2373 with Matrix-M prime-only groups of mice exhibited a dose-dependent reduction in virus titer, with recipients of the 10 μg dose having no detectable virus at day 4 post infection. Mice receiving 1 μg, 0.1 μg, and 0.01 μg doses all showed a marked reduction in titer compared to placebo-vaccinated mice. In the prime/boost groups, mice immunized with 10 μg, 1 μg, and 0.1 μg doses had almost undetectable lung virus loads. These results confirmed that NVX-CoV2373 confers protection against SARS-CoV-2 and that low doses of the vaccine associated with lower serologic responses do not exacerbate weight loss or induce exaggerated illness. (Tian et al., 2021)