An enveloped virus-like particle vaccine expressing a stabilized prefusion form of the SARS-CoV-2 spike protein elicits potent immunity after a single dose

Abstract

Development of efficacious single dose vaccines would substantially aid efforts to stop the uncontrolled spread of the COVID-19 pandemic. We evaluated enveloped virus-like particles (eVLPs) expressing various forms of the SARS-CoV-2 spike protein and several adjuvants in an effort to identify a COVID-19 vaccine candidate efficacious after a single dose. The eVLPs expressing a modified prefusion form of SARS-CoV-2 spike protein were selected as they induced the highest antibody binding titers and neutralizing activity after a single injection in mice. Formulation of SARS-CoV-2 S eVLPs with aluminum phosphate resulted in balanced induction of IgG2 and IgG1 isotypes and antibody binding and neutralization titers were undiminished for more than 3 months after a single immunization. A single dose of this candidate, VBI-2902a (prefusion S eVLPs formulated with aluminum phosphate), protected Syrian golden hamsters from challenge with SARS-CoV-2 and supports the on-going clinical evaluation of VBI-2902a as a potential single dose vaccine against COVID-19.

A thermostable oral SARS-CoV-2 vaccine induces mucosal and protective immunity

“…Indeed, when vaccines are administered i.m., VSP-e-VLP always led to higher titers of antibodies than their plain e-VLPs. Of note, a SARS-CoV-2 VLP based on our platform technology 15 was independently reported to generate a good NAb response after i.m. administration, but with no reports of IgA at mucosal sites.…”

“…This requires a suitable production of vaccine with an excellent safety profile. Noteworthy, we contributed to the design of an anti-CMV e-VLP vaccine based on our e-VLP platform that has already been used in patients, demonstrating scalable GMP production and an excellent safety profile 15,17,46 .…”

“…As NAbs are mostly targeted to conformational structures, e-VLPs are thus particularly suitable for NAb induction 12 . We previously showed that such e-VLPs could generate robust NAbs against many viruses, such as influenza, HCV and CMV, in mice, macaques and humans [13][14][15][16][17] . Moreover, exploiting the versatile engineering possibilities for these e-VLPs, we recently showed that they could be harnessed with variable surface proteins (VSPs) from the intestinal parasite Giardia lamblia, affording them resistance to degradation and the triggering of robust mucosal cellular and antibody immune responses after oral administration 18,19 .…”

VLP-Based COVID-19 Vaccines: An Adaptable Technology against the Threat of New Variants

“…The NDVLP-S2P (Figure 5B) is a heterologous chimeric eVLP vaccine candidate against SARS-CoV-2 that uses the structure of a well-characterized enveloped virus, the Newcastle disease virus (NDV) [41], and is being developed by the National Institute of Allergy and Infectious Diseases (NIAID). The transmembrane domain of the NDV fusion protein was fused to SARS-CoV-2 S2P, allowing the correct display of S2P on the VLP surface [41,45,149]. The NDV-S2P VLPs were more immunogenic than the trimeric S protein alone, showing that the presentation of antigens on the surface of the VLPs is advantageous [41].…”

“…This vaccine candidate is already in phase 3 clinical trials (NCT04636697). VBI-2902a [149] is an MLV-based eVLPs vaccine candidate containing the S protein in the prefusion state fused with the VSV-G transmembrane cytoplasmic domain (VSV-GTC) (Figure 5D). This vaccine is being developed by VBI Vaccines and is in ongoing clinical trials 1/2 (NCT04773665).…”