Elicitation of potent neutralizing antibodies in obese mice by ISA 51-adjuvanted SARS-CoV-2 spike RBD-Fc vaccine

Abstract

Vaccination is considered to be the most effective countermeasure to prevent and combat the global health threats of COVID-19. People with obesity are at a greater risk of hospitalization, life-threatening illness, and adverse outcomes after having COVID-19. Therefore, a safe and effective COVID-19 vaccine for obese individuals is urgently needed. In the study, the vaccine composed of the ISA 51 adjuvant and the SARS-CoV-2 spike (S) receptor-binding domain (RBD) in conjugation with the human IgG1 Fc fragment (named as ISA 51-adjuvanted RBD-Fc vaccine) was developed and inoculated in the regular chow diet (RCD) lean mice and the high-fat diet (HFD)-induced obese mice. The S protein-specific IgG titers were largely induced in an increasing manner along with three doses of ISA 51-adjuvanted RBD-Fc vaccine without causing any harmful side effect. In the HFD mice, the S protein-specific IgG titers can be quickly observed 2 weeks post the first inoculation. The antisera elicited by the ISA 51-adjuvanted RBD-Fc vaccine in the RCD and HFD mice exhibited potent SARS-CoV-2 neutralizing activities in the plaque reduction neutralization test (PRNT) assays and showed similar specificity for recognizing the key residues in the RBD which were involved in interacting with angiotensin-converting enzyme 2 (ACE2) receptor. The immune efficacy of the ISA 51-adjuvanted RBD-Fc vaccine in the HFD mice can be sustainably maintained with the PRNT50 values of 1.80–1.91×10 −3 for at least 8 weeks post the third inoculation. Collectively, the RBD-Fc-based immunogen and the ISA 51-adjuvanted formulation can be developed as an effective COVID-19 vaccine for obese individuals. Key Points • The ISA 51-adjuvanted RBD-Fc vaccine can induce potent SARS-CoV-2 neutralizing antibodies in the obese mouse • The antibodies elicited by the ISA 51-adjuvanted RBD-Fc vaccine can bind to the key RBD residues involved in interacting with ACE2 • The immune efficacy of the ISA 51-adjuvanted RBD-Fc vaccine can be sustainably maintained for at least 8 weeks post the third inoculation

CHO-produced RBD-Fc subunit vaccines with alternative adjuvants generate immune responses against SARS-CoV-2

“…This implied that RBD-based vaccine could elicit sufficient neutralizing antibodies when compared to whole spike candidate. These results were also consistent with other reports of RBD-Fc-based vaccine development that RBD-Fc shows high potency as vaccine candidate against SARS-CoV-2 [17,[19][20][21][22][23][24].…”

“…Combining these results with the result of primary structure analysis using MS/MS, it was confirmed that CHO-produced RBD-Fc could display native-like properties. This results also were consistent with previous studies where RBD-Fc vaccine obtained from mammalian cell expression system exhibited desired biochemical characteristics [19][20][21]24].…”

“…Hence, Th2-polarized immune responses from RBD-Fc with Montanide ISA51 could be reduced, implying balanced Th1/Th2 responses. Moreover, RBD-Fc with Montanide ISA51 vaccine showed potent immune responses in obese mice, suggesting that this formulation is safe and effective for conditioned individual [20]. Another formulation, Montanide ISA720, formulated with CHO-produced RBD-Fc vaccine has entered clinical study, suggesting a promising use of this water in oil emulsion system in combating SARS-CoV-2 [25].…”

“…It was shown that the vaccine candidate is effective in viral protection in non-human primates and is now under Phase 2 clinical trial [18]. Additionally, RBD fused with human IgG Fc fragment (RBD-Fc) has been studied for SARS-CoV-2 vaccine development since it could enhance immunogenicity of RBD and its half-life [19][20][21][22][23][24]. Currently, at least two RBD-Fc-based vaccine candidates have been investigated in clinical trial studies including AKS-452 and Betuvax-CoV-2 [24,25] and evidence suggests that RBD-based subunit vaccines are indeed promising candidates.…”