Development and preclinical evaluation of virus‐like particle vaccine against COVID‐19 infection

Abstract

Background Vaccines that incorporate multiple SARS‐CoV‐2 antigens can further broaden the breadth of virus‐specific cellular and humoral immunity. This study describes the development and immunogenicity of SARS‐CoV‐2 VLP vaccine that incorporates the four structural proteins of SARS‐CoV‐2. Methods VLPs were generated in transiently transfected HEK293 cells, purified by multimodal chromatography, and characterized by tunable‐resistive pulse sensing, AFM, SEM, and TEM. Immunoblotting studies verified the protein identities of VLPs. Cellular and humoral immune responses of immunized animals demonstrated the immune potency of the formulated VLP vaccine. Results Transiently transfected HEK293 cells reproducibly generated vesicular VLPs that were similar in size to and expressing all four structural proteins of SARS‐CoV‐2. Alum adsorbed, K3‐CpG ODN‐adjuvanted VLPs elicited high titer anti‐S, anti‐RBD, anti‐N IgG, triggered multifunctional Th1‐biased T‐cell responses, reduced virus load, and prevented lung pathology upon live virus challenge in vaccinated animals. Conclusion These data suggest that VLPs expressing all four structural protein antigens of SARS‐CoV‐2 are immunogenic and can protect animals from developing COVID‐19 infection following vaccination.

SARS-CoV-2 Virus-like Particles Produced by a Single Recombinant Baculovirus Generate Anti-S Antibody and Protect against Variant Challenge

“…The emergence of SARS-CoV-2 into the human population, most likely by spill over from a zoonotic reservoir [ 54 ], has led to the rapid development and licensing of several efficacious vaccines including those based on inactivated virus, adenovirus vectors, or direct nucleic acid [ 19 , 55 , 56 ]. Other experimental vaccines, including VLP and VLP-like vaccines have also been reported [ 48 , 57 , 58 , 59 , 60 ]. Based on a previously described VLP of SARS CoV-2 [ 9 ] we report here the development and test of a VLP for SARS-CoV-2 based on the co-expression of the S, M and E proteins using the baculovirus expression system.…”

“…VLPs made by co-expression of all four structural proteins in mammalian cells, have been used to investigate the basis of genome packaging and, in turn, the role of variant sequences on the efficiency of SARS-CoV-2 virus assembly, providing evidence that amino acid changes in N rather than S are significant drivers of variant emergence [ 67 ]. Yilmaz et al have also described VLPs from mammalian cells based on all four structural proteins and demonstrated superior immune responses following immunization of mice, rats and ferrets but these VLPs were adsorbed to alum and contained a CpG adjuvant prior to immunization [ 60 ]. The responses reduced but do not prevent challenge virus infection when used in a hACE2 transgenic (tg) mouse model but significantly reduced lung pathology, similar to the data reported here [ 60 ].…”

Intranasal Immunization with a Proteosome-Adjuvanted SARS-CoV2 Spike Protein-Based Vaccine is Immunogenic and Efficacious in Mice & Hamsters

“…Controls included mice injected with the vaccine vehicle, phosphate-buffered saline (PBS), or SmT1v3 adjuvanted with aluminum phosphate (AdjuPhos TM ). Aluminum phosphate is a conventional vaccine adjuvant found in a number of approved vaccines and is a potent inducer of antigen-specific antibody responses 26,27 . SmT1v3-AdjuPhos TM formulations were delivered intramuscularly 28 .…”

Development of DNA Vaccine Candidate against SARS-CoV-2

“…Hence, both subunits have their distinct functions in the progression of viral entry and infection. In vaccine development, for the prefusion-stabilization of S-protein six, proline substitution (HexaPro) is often performed as it elicits higher expression and resistance to various temperature conditions, which gives better stability [ 19 , 20 ]. Additionally, D614G mutation in S-protein demonstrates the augmented susceptibility of SARS-CoV-2 to neutralization [ 21 ].…”