A recombinant subunit vaccine candidate produced in plants elicits neutralizing antibodies against SARS-CoV-2 variants in macaques

Abstract

Since the outbreak of the coronavirus disease (COVID) pandemic in 2019, the development of effective vaccines to combat the infection has been accelerated. With the recent emergence of highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC), there are concerns regarding the immune escape from vaccine-induced immunity. Hence an effective vaccine against VOC with a potent immune response is required. Our previous study confirmed that the two doses of the plant-produced receptor-binding domain (RBD) of SARS-CoV-2 fused with the Fc region of human IgG1, namely Baiya SARS-CoV-2 Vax 1, showed high immunogenicity in mice and monkeys. Here, we aimed to evaluate the immunogenicity of a three-dose intramuscular injection of Baiya SARS-CoV-2 Vax 1 on days 0, 21, and 133 in cynomolgus monkeys. At 14 days after immunization, blood samples were collected to determine RBD-specific antibody titer, neutralizing antibody, and pseudovirus neutralizing antibody titers. Immunized monkeys developed significantly high levels of antigen-specific antibodies against SARS-CoV-2 compared to the control group. Interestingly, the sera collected from immunized monkeys also showed a neutralizing antibody response against the SARS-CoV-2 VOCs; Alpha, Beta, Gamma, Delta, and Omicron. These findings demonstrate that a three-dose regimen of Baiya SARS-CoV-2 Vax 1 vaccine elicits neutralizing immune response against SARS-CoV-2 variants.

Intranasal Boosting with Spike Fc-RBD of Wild-Type SARS-CoV-2 Induces Neutralizing Antibodies against Omicron Subvariants and Reduces Viral Load in the Nasal Turbinate of Mice

“…Instead of the whole spike protein, some just used the spike RBD to minimize the amount of non-neutralizing antigenic epitope and the associated antigenic sin. Others tried to change the amino acid residues around the RBD to improve immunogenicity by using the RBD (F318-C617) [ 34 ], RBD (R319-F541) [ 35 ], RBD (N331-V524) [ 36 , 37 , 38 , 39 ], RBD (P330-E583) [ 40 ], RBD (R319-F541) [ 41 ], and RBD (Arg319-N532) [ 29 ] protein as the immunogen. Others added glycosylation sites around the RBD to shield the non-neutralizing epitopes of the RBD [ 42 ].…”

“…In this study, we used a Fc-linked trimeric spike RBD to improve the uptake and presentation of the trimeric spike RBD, and we used intranasal administration to achieve a more robust immunity in the upper airway. Twelve studies [ 29 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 43 , 44 , 45 ] have tried to use Fc-RBD subcutaneously or intramuscularly with mostly alum, one Freund’s, one MF59, manganese, or Montanide TM ISA720 adjuvants in mice, and one non-human primate model; but only one study has used intranasal vaccination in Balb/c mice, and it did not try to use it for boosting after priming with intramuscular inactivated vaccine.…”

Plants as Biofactories for Therapeutic Proteins and Antiviral Compounds to Combat COVID-19

“…A publication on preclinical results states that the RBD protein has been modified by fusing it with the Fc region [ 51 ]. When used with alum as adjuvant, Vax 1 induced potent immunological responses in both mice and cynomolgus monkeys [ 69 , 77 , 78 ]. Vax 1 was also reported to show 100% efficacy against infection in K18-hACE2 mice [ 79 ].…”

Advancements in Vaccination Strategies: From Historical Milestones to Modern Innovations in Viral Disease Prevention and Public Health

“…mRNA vaccines for COVID-19 developed by Pfizer-BioNTech and Moderna (Kracalik et al, 2022), Viral vector vaccines developed by Oxford-AstraZeneca and Johnson & Johnson for COVID-19. Similarly, Many substances including lipids, metal and nonmetal inorganics, various polymers, and virus-like particles (VLPs) can be used to develop vaccines based on nanoparticles (Lu et al, 2023) and vaccines like Medicago Covifenz® COVID-19 vaccine have been developed using plant-based technologies (Phoolcharoen et al, 2023). This vaccine mimics the virus and stimulates the immune system without spreading illness by leveraging the plant's natural cell mechanism to create non-infectious VLPs (Ma et al, 2023;Trad & El Falou, 2022).…”