Nuvaxovid

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is associated with a spectrum of illness from asymptomatic infection to a severe disease requiring hospitalization and supplemental oxygen and can be fatal. The SARS-CoV-2 spike (S) protein is a class I fusion glycoprotein with an RRAR furin-like cleavage site that gives rise to the S2 stalk and S1 cap; non-covalent assembly of three S1/S2 protomers gives rise to the functional S-trimer. Upon binding to its receptor, human angiotensin-converting enzyme 2 (hACE2), the S protein undergoes significant structural rearrangement to expose the hydrophobic fusion peptide that mediates membrane fusion and intracellular viral particle release. The S-hACE2 interaction, therefore, represents a critical step in SARS-CoV-2 infection.

Given the important role of the S protein in infection, active immunization with S protein mRNA or protein variants remains an important strategy in controlling COVID-19. Nuvaxovid comprises a recombinant S protein, with a mutated furin-like cleavage site (682-QQAQ-685) and two proline substitutions (K986P and V987P), produced using Sf9 cells, together with a saponin-based Matrix-M adjuvant. The recombinant S protein forms thermostable 27.2 nm nanoparticles that bind hACE2 with an IC50 of 18 ng mL-1. Active immunization in mice with 0.1-10 μg S protein/5 μg Matrix-M had significantly higher anti-S IgG titers, higher CD4+/CD8+ effector cells counts, higher germinal centre Tfh/B cell counts, higher levels of type I (IFN-γ) and type II (IL-4 and IL-5) cytokines, and decreased viral load; these metrics were associated with improved lung histopathology. Similar results were obtained in non-human primates and human volunteers during phase I/II clinical trials.

Overall, nuvaxovid, given as a two-dose regimen with Matrix-M adjuvant, appears to induce mature antibody subclass (IgG/IgA) production and a general trend towards a Th1 over a Th2 cellular immune response.