Protective immunity induced by COVID-19 vaccines is mediated mainly by spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we report the development of a recombinant prefusion stabilized SARS-CoV-2 spike protein-subunit-based COVID-19 vaccine produced in the mammalian cell line. The gene encoding ectodomain (ECD) of the spike protein was engineered and cloned into Freedom pCHO 1.0, a mammalian expression vector, and subsequently expressed in the Chinese Hamster Ovary suspension cell line (CHO-S).The recombinant S protein ectodomain (hereafter referred to as IMT-CVAX) was purified using a combination of tangential flow filtration and liquid chromatography. Biochemical and biophysical characterization of IMT-CVAX was done to ensure its vital quality attributes. Intramuscular immunization of mice with two doses of adjuvanted IMT-CVAX elicited a strong anti-Spike IgG response.In pseudovirus-based assays, IMT-CVAX immune mice sera exhibited a broad-spectrum neutralization of several SARS-CoV-2 variants of concern (VoCs). Golden Syrian Hamster immunized with IMT-CVAX provided excellent protection against SARS-CoV-2 infection, and, hamster immune sera neutralized the live SARS-CoV-2 virus.The adjuvanted IMT-CVAX induced robust Tfh-cells response and germinal center (GC) reaction in human ACE2 receptor-expressing transgenic mice. The findings of this study may pave the way for developing next-generation protein subunit-based vaccines to combat the existing SARS-CoV-2 and its emerging VoCs. The IMT-CVAX is produced using a scalable process and can be used for large-scale vaccine production in an industrial setup.

The Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has taken its toll on worldwide public health infrastructure. SARS-CoV-2 is reported to exhibit wide tissue tropism, contributing to its severe pathogenicity that often culminates in multiple-organ failure. The onslaught of this disease has intensified due to the emergence of variants of concern (VOC), such as Delta and Omicron. These variants have been linked to gastrointestinal (GI) symptoms, suggesting a potential fecal-oral route of viral transmission. Here we compared the broad tissue tropism of ancestral Hong-Kong SARS-CoV-2 (SARS-CoV-2 HK) against Delta and Omicron VOCs in aa hamster model by analyzing tissue samples collected from the upper and lower respiratory system and the GI tract. We observed an overall increase in vRNA load and pro-inflammatory cytokines, especially in GI tracts of animals infected with Delta virus, indicating selective virus tropism and pathology in these tissues. However, no apparent spike in Delta viral load was observed in the large intestine and fecal matter. Overall, our research investigates the wide range of tissues that various SARS-CoV-2 strains can infect in hamsters and presents evidence supporting the increased preference of Delta VOCs for infecting the GI tract.