A recombinant spike protein subunit vaccine confers protective immunity against SARS-CoV-2 infection and transmission in hamsters

Abstract

Multiple safe and effective vaccines that elicit immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary to respond to the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here, we developed a protein subunit vaccine comprised of spike ectodomain protein (StriFK) plus a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant (FH002C). StriFK-FH002C generated substantially higher neutralizing antibody titers in mice, hamsters, and cynomolgus monkeys than those observed in plasma isolated from COVID-19 convalescent individuals. StriFK-FH002C also induced both Th1- and Th2-polarized helper T cell responses in mice. In hamsters, StriFK-FH002C immunization protected animals against SARS-CoV-2 challenge, as shown by absence of virus-induced weight loss, fewer symptoms of disease, and reduced lung pathology. Vaccination of hamsters with StriFK-FH002C also reduced within-cage virus transmission to unvaccinated, cohoused hamsters. In summary, StriFK-FH002C represents an effective, protein subunit-based SARS-CoV-2 vaccine candidate.

An adjuvanted subunit SARS-CoV-2 spike protein vaccine provides protection against Covid-19 infection and transmission

“…Hence, these other COVID-19 vaccines do not appear to induce significant mucosal protection. Modest protection was observed after immunization with a subunit spike protein vaccine with a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant (FH002C) where after three doses of vaccine a 50% reduction in virus transmission to naive contact animals was observed 28 . The protection against transmission we observed in our study in the SWE-adjuvated rSpike protein group was consistent with the lack of detectable infectious virus in Day 2 oropharyngeal swabs and Day 3 nasal turbinates and lungs, normally the time where peak virus replication occurs in the hamster model 29 .…”

Two-Component Nanoparticle Vaccine Displaying Glycosylated Spike S1 Domain Induces Neutralizing Antibody Response against SARS-CoV-2 Variants

“…This is relatively low, although production yields of prefusion-stabilized S vary greatly between expression systems. Yields of 0.5 mg/liter S have been reported for FreeStyle 293 cells ( 10 ), 5 mg/liter for HEK293 cells ( 56 ), and up to 200 mg/liter for stably transfected CHO cells ( 57 ). Whereas trimeric S is often unstable ( 58 , 59 ), smaller spike protein domains, for example, S1 or RBD, are generally more stable and result in higher yields.…”

Follicular Helper T Cells in the Immunopathogenesis of SARS-CoV-2 Infection

“…These findings have indicated that SARS-CoV-2 mRNA vaccines can effectively promote antigen-specific Tfh cell differentiation, B cell responses and the generation of protective antibodies, which are considered as promising candidates for eliciting high-quality adaptive immune responses to control and clear SARS-CoV-2 infection. Additionally, the specific protein vaccines including SARS-CoV-2 subunit vaccine (NVX-CoV2373) with the full-length spike (S) protein, StriFK-FH002C and Spike (S)/receptor binding domain (RBD) protein subunit vaccine significantly induce specific cTfh cell and GC B cell responses, resulting in high neutralizing antibody titers of SARS-CoV-2 ( 170 – 172 ) ( Table 3 ). Various clinical trials in humans indicate that inactivated SARS-CoV-2 vaccines can induce satisfactory high neutralizing antibody titers that notably reduce the number of patients with severe COVID-19 ( 173 – 176 ).…”