Immunogenicity and pre-clinical efficacy of an OMV-based SARS-CoV-2 vaccine

Grandi, Alberto; Tomasi, Michele; Ullah, Irfan; Bertelli, Cinzia; Vanzo, Teresa; Accordini, Silvia; Gagliardi, Assunta; Zanella, Ilaria; Benedet, Mattia; Corbellari, Riccardo; Lascio, Gabriele Di; Tamburini, Silvia; Caproni, Elena; Croia, Lorenzo; Ravà, Micol; Fumagalli, Valeria; Lucia, Pietro Di; Marotta, Davide; Sala, Eleonora; Iannacone, Matteo; Kumar, Priti; Mothes, Walther; Uchil, Pradeep D.; Cherepanov, Peter; Bolognesi, M.; Pizzato, Massimo; Grandi, Guido

doi:10.21203/rs.3.rs-2788726/v1

Cited by 3 publications

(1 citation statement)

References 34 publications

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“…The candidate vaccine was also protective in a hamster challenge model. OMVs engineered to incorporate peptides derived from the receptor binding motif (RBM) of the spike protein from SARS-CoV-2 have also been made and shown to elicit neutralizing antibodies in mice [ 92 ].…”

Section: Trends Emerging In Preclinical Studiesmentioning

confidence: 99%

Outer Membrane Vesicle Vaccine Platforms

Micoli,

Adamo,

Nakakana

2023

BioDrugs

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Outer membrane vesicles (OMVs) are spontaneously released by many gram-negative bacteria during their growth and constitute an important virulence factor for bacteria, helping them to survive through harsh environmental conditions. Native OMVs, naturally-released from bacteria, are produced at a level too low for vaccine manufacturing, requiring chemical treatment (detergent-extracted) or genetic manipulation, resulting in generalized modules for membrane antigens (GMMAs). Over the years, the nature and properties of OMVs have made them a viable platform for vaccine development. There are a few licensed OMV vaccines mainly for the prevention of meningitis caused by Neisseria meningitidis serogroup B (MenB) and Haemophilus influenzae type b (Hib). There are several candidates in clinical development against other gram-negative organisms from which the OMVs are derived, but also against heterologous targets in which the OMVs are used as carriers (e.g. coronavirus disease 2019 [COVID-19]). The use of OMVs for targets other than those from which they are derived is a major advancement in OMV technology, improving its versatility by being able to deliver protein or polysaccharide antigens. Other advances include the range of genetic modifications that can be made to improve their safety, reduce reactogenicity, and increase immunogenicity and protective efficacy. However, significant challenges remain, such as identification of general tools for high-content surface expression of heterologous proteins on the OMV surface. Here, we outline the progress of OMV vaccines to date, particularly discussing licensed OMV-based vaccines and candidates in clinical development. Recent trends in preclinical research are described, mainly focused on genetic manipulation and chemical conjugation for the use of OMVs as carriers for heterologous protein and polysaccharide antigens. Remaining challenges with the use of OMVs and directions for future research are also discussed.

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Section: Trends Emerging In Preclinical Studiesmentioning

confidence: 99%

Outer Membrane Vesicle Vaccine Platforms

Micoli,

Adamo,

Nakakana

2023

BioDrugs

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Bacterial Outer Membrane Vesicles as a Platform for the Development of a Broadly Protective Human Papillomavirus Vaccine Based on the Minor Capsid Protein L2

Tamburini,

Zhang,

Gagliardi

et al. 2023

Vaccines

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Human papillomaviruses (HPVs) are a large family of viruses with a capsid composed of the L1 and L2 proteins, which bind to receptors of the basal epithelial cells and promote virus entry. The majority of sexually active people become exposed to HPV and the virus is the most common cause of cervical cancer. Vaccines are available based on the L1 protein, which self-assembles and forms virus-like particles (VLPs) when expressed in yeast and insect cells. Although very effective, these vaccines are HPV type-restricted and their costs limit broad vaccination campaigns. Recently, vaccine candidates based on the conserved L2 epitope from serotypes 16, 18, 31, 33, 35, 6, 51, and 59 were shown to elicit broadly neutralizing anti-HPV antibodies. In this study, we tested whether E. coli outer membrane vesicles (OMVs) could be successfully decorated with L2 polytopes and whether the engineered OMVs could induce neutralizing antibodies. OMVs represent an attractive vaccine platform owing to their intrinsic adjuvanticity and their low production costs. We show that strings of L2 epitopes could be efficiently expressed on the surface of the OMVs and a polypeptide composed of the L2 epitopes from serotypes 18, 33, 35, and 59 provided a broad cross-protective activity against a large panel of HPV serotypes as determined using pseudovirus neutralization assay. Considering the simplicity of the OMV production process, our work provides a highly effective and inexpensive solution to produce universal anti-HPV vaccines.

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Toward a SARS-CoV-2 VLP Vaccine: HBc/G as a Carrier for SARS-CoV-2 Spike RBM and Nucleocapsid Protein-Derived Peptides

Petrovskis,

Skrastina,

Jansons

et al. 2024

Vaccines

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Virus-like particles (VLPs) offer an attractive possibility for the development of vaccines. Recombinant core antigen (HBc) of Hepatitis B virus (HBV) was expressed in different systems, and the E. coli expression system was shown to be effective for the production of HBc VLPs. Here, we used HBc of the HBV genotype G (HBc/G) as a technologically promising VLP carrier for the presentation of spike RBM and nucleocapsid protein-derived peptides of the SARS-CoV-2 Delta variant for subsequent immunological evaluations of obtained fusion proteins. The major immunodominant region (MIR) of the HBc/G protein was modified through the insertion of a receptor binding motif (RBM) from the S protein or B-cell epitope-containing peptide from the N protein. The C-terminus of the two truncated HBc/G proteins was used for the insertion of a group of five cytotoxic T lymphocyte (CTL) epitopes from the N protein. After expression in E. coli, the MIR-derived proteins were found to be insoluble and were recovered through step-wise solubilization with urea, followed by refolding. Despite the lack of correct VLPs, the chimeric proteins induced high levels of antibodies in BALB/c mice. These antibodies specifically recognized either eukaryotically expressed hRBD or bacterially expressed N protein (2–220) of SARS-CoV-2. CTL-epitope-containing proteins were purified as VLPs. The production of cytokines was analyzed through flow cytometry after stimulation of T-cells with target CTL peptides. Only a protein with a deleted polyarginine (PA) domain was able to induce the specific activation of T-cells. At the same time, the T-cell response against the carrier HBc/G protein was detected for both proteins. The neutralization of SARS-CoV-2 pseudotyped murine retrovirus with anti-HBc/G-RBM sera was found to be low.

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Immunogenicity and pre-clinical efficacy of an OMV-based SARS-CoV-2 vaccine

Cited by 3 publications

References 34 publications

Outer Membrane Vesicle Vaccine Platforms

Outer Membrane Vesicle Vaccine Platforms

Bacterial Outer Membrane Vesicles as a Platform for the Development of a Broadly Protective Human Papillomavirus Vaccine Based on the Minor Capsid Protein L2

Toward a SARS-CoV-2 VLP Vaccine: HBc/G as a Carrier for SARS-CoV-2 Spike RBM and Nucleocapsid Protein-Derived Peptides

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