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Chimeric coronavirus-like particles carrying severe acute respiratory syndrome coronavirus (SCoV) S protein protect mice against challenge with SCoV.

ABSTRACT: We tested the efficacy of coronavirus-like particles (VLPs) for protecting mice against severe acute respiratory syndrome coronavirus (SCoV) infection. Coexpression of SCoV S protein and E, M and N proteins of mouse hepatitis virus in 293T or CHO cells resulted in the efficient production of chimeric VLPs carrying SCoV S protein. Balb/c mice inoculated with a mixture of chimeric VLPs and alum twice at an interval of four weeks were protected from SCoV challenge, as indicated by the absence of infectious virus in the lungs. The same groups of mice had high levels of SCoV-specific neutralizing antibodies, while mice in the negative control groups, which were not immunized with chimeric VLPs, failed to manifest neutralizing antibodies, suggesting that SCoV-specific neutralizing antibodies are important for the suppression of viral replication within the lungs. Despite some differences in the cellular composition of inflammatory infiltrates, we did not observe any overt lung pathology in the chimeric-VLP-treated mice, when compared to the negative control mice. Our results show that chimeric VLP can be an effective vaccine strategy against SCoV infection.

SUBMITTER: Lokugamage KG

PROVIDER: S-EPMC2267761 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Chimeric severe acute respiratory syndrome coronavirus (SARS-CoV) S glycoprotein and influenza matrix 1 efficiently form virus-like particles (VLPs) that protect mice against challenge with SARS-CoV.

Project description:SARS-CoV was the cause of the global pandemic in 2003 that infected over 8000 people in 8 months. Vaccines against SARS are still not available. We developed a novel method to produce high levels of a recombinant SARS virus-like particles (VLPs) vaccine containing the SARS spike (S) protein and the influenza M1 protein using the baculovirus insect cell expression system. These chimeric SARS VLPs have a similar size and morphology to the wild type SARS-CoV. We tested the immunogenicity and protective efficacy of purified chimeric SARS VLPs and full length SARS S protein vaccines in a mouse lethal challenge model. The SARS VLP vaccine, containing 0.8 μg of SARS S protein, completely protected mice from death when administered intramuscular (IM) or intranasal (IN) routes in the absence of an adjuvant. Likewise, the SARS VLP vaccine, containing 4 μg of S protein without adjuvant, reduced lung virus titer to below detectable level, protected mice from weight loss, and elicited a high level of neutralizing antibodies against SARS-CoV. Sf9 cell-produced full length purified SARS S protein was also an effective vaccine against SARS-CoV but only when co-administered IM with aluminum hydroxide. SARS-CoV VLPs are highly immunogenic and induce neutralizing antibodies and provide protection against lethal challenge. Sf9 cell-based VLP vaccines are a potential tool to provide protection against novel pandemic agents.

| S-EPMC3165014 | biostudies-literature

Immune responses against severe acute respiratory syndrome coronavirus induced by virus-like particles in mice.

Project description:Virus-like particles (VLPs) represent a promising vaccine against severe acute respiratory syndrome coronavirus (SARS CoV). In this study, recombinant baculovirus vAcS and vAcME were constructed to express the S protein and the M and E proteins of SARS CoV, respectively. Electron microscope analysis demonstrated the formation of VLPs in vAcME and vAcS coinfected insect cells. Mice immunized four times with VLPs developed high antibody titres against SARS CoV. In addition, VLPs elicited cell-mediated immunity as demonstrated by enhanced interferon-gamma and interleukin-4 production. VLPs also conferred protective immunity against the infection of Spike protein pseudotyped murine leukaemia virus. Our findings demonstrate that SARS CoV VLPs are immunogenic and can elicit strong SARS CoV-specific humoral and cellular immune responses in mice. This is the first study describing the immunogenicity of SARS CoV VLPs, providing valuable data for developing a protective vaccine against SARS CoV infection.

| S-EPMC2266036 | biostudies-literature

Assembly of human severe acute respiratory syndrome coronavirus-like particles.

Project description:Viral particles of human severe acute respiratory syndrome coronavirus (SARS CoV) consist of three virion structural proteins, including spike protein, membrane protein, and envelope protein. In this report, virus-like particles were assembled in insect cells by the co-infection with recombinant baculoviruses, which separately express one of these three virion proteins. We found that the membrane and envelope proteins are sufficient for the efficient formation of virus-like particles and could be visualized by electron microscopy. Sucrose gradient purification followed by Western blot analysis and immunogold labeling showed that the spike protein could be incorporated into the virus like particle also. The construction of engineered virus-like particles bearing resemblance to the authentic one is an important step towards the development of an effective vaccine against infection of SARS CoV.

| S-EPMC7111196 | biostudies-literature

Oral Vaccination Protects Against Severe Acute Respiratory Syndrome Coronavirus 2 in a Syrian Hamster Challenge Model.

Project description:BackgroundVaccines that are shelf stable and easy to administer are crucial to improve vaccine access and reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission around the world.MethodsIn this study, we demonstrate that an oral, adenovirus-based vaccine candidate protects against SARS-CoV-2 in a Syrian hamster challenge model.ResultsHamsters administered 2 doses of VXA-CoV2-1 showed a reduction in weight loss and lung pathology and had completely eliminated infectious virus 5 days postchallenge. Oral immunization induced antispike immunoglobulin G, and neutralizing antibodies were induced upon oral immunization with the sera, demonstrating neutralizing activity.ConclusionsOverall, these data demonstrate the ability of oral vaccine candidate VXA-CoV2-1 to provide protection against SARS-CoV-2 disease.

| S-EPMC8689930 | biostudies-literature

Successful vaccination strategies that protect aged mice from lethal challenge from influenza virus and heterologous severe acute respiratory syndrome coronavirus.

Project description:Newly emerging viruses often circulate as a heterogeneous swarm in wild animal reservoirs prior to their emergence in humans, and their antigenic identities are often unknown until an outbreak situation. The newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV) and reemerging influenza virus cause disproportionate disease in the aged, who are also notoriously difficult to successfully vaccinate, likely due to immunosenescence. To protect against future emerging strains, vaccine platforms should induce broad cross-reactive immunity that is sufficient to protect from homologous and heterologous challenge in all ages. From initial studies, we hypothesized that attenuated Venezuelan equine encephalitis virus (VEE) replicon particle (VRP) vaccine glycoproteins mediated vaccine failure in the aged. We then compared the efficacies of vaccines bearing attenuated (VRP(3014)) or wild-type VEE glycoproteins (VRP(3000)) in young and aged mice within novel models of severe SARS-CoV pathogenesis. Aged animals receiving VRP(3000)-based vaccines were protected from SARS-CoV disease, while animals receiving the VRP(3014)-based vaccines were not. The superior protection for the aged observed with VRP(3000)-based vaccines was confirmed in a lethal influenza virus challenge model. While the VRP(3000) vaccine's immune responses in the aged were sufficient to protect against lethal homologous and heterologous challenge, our data suggest that innate defects within the VRP(3014) platform mediate vaccine failure. Exploration into the mechanism(s) of successful vaccination in the immunosenescent should aid in the development of successful vaccine strategies for other viral diseases disproportionately affecting the elderly, like West Nile virus, influenza virus, norovirus, or other emerging viruses of the future.

| S-EPMC3014161 | biostudies-literature

A replication-incompetent Rift Valley fever vaccine: chimeric virus-like particles protect mice and rats against lethal challenge.

Project description:Virus-like particles (VLPs) present viral antigens in a native conformation and are effectively recognized by the immune system and therefore are considered as suitable and safe vaccine candidates against many viral diseases. Here we demonstrate that chimeric VLPs containing Rift Valley fever virus (RVFV) glycoproteins G(N) and G(C), nucleoprotein N and the gag protein of Moloney murine leukemia virus represent an effective vaccine candidate against Rift Valley fever, a deadly disease in humans and livestock. Long-lasting humoral and cellular immune responses are demonstrated in a mouse model by the analysis of neutralizing antibody titers and cytokine secretion profiles. Vaccine efficacy studies were performed in mouse and rat lethal challenge models resulting in high protection rates. Taken together, these results demonstrate that replication-incompetent chimeric RVF VLPs are an efficient RVFV vaccine candidate.

| S-EPMC2813982 | biostudies-literature

Biomimetic Virus-Like Particles as Severe Acute Respiratory Syndrome Coronavirus 2 Diagnostic Tools.

Project description:Coronavirus disease 2019 (COVID-19) is a highly transmissible disease that has affected more than 90% of the countries worldwide. At least 17 million individuals have been infected, and some countries are still battling first or second waves of the pandemic. Nucleic acid tests, especially reverse transcription polymerase chain reaction (RT-PCR), have become the workhorse for early detection of COVID-19 infection. Positive controls for the molecular assays have been developed to validate each test and to provide high accuracy. However, most available positive controls require cold-chain distribution and cannot serve as full-process control. To overcome these shortcomings, we report the production of biomimetic virus-like particles (VLPs) as SARS-CoV-2 positive controls. A SARS-CoV-2 detection module for RT-PCR was encapsidated into VLPs from a bacteriophage and a plant virus. The chimeric VLPs were obtained either by in vivo reconstitution and coexpression of the target detection module and coat proteins or by in vitro assembly of purified detection module RNA sequences and coat proteins. These VLP-based positive controls mimic SARS-CoV-2 packaged ribonucleic acid (RNA) while being noninfectious. Most importantly, we demonstrated that the positive controls are scalable, stable, and can serve broadly as controls, from RNA extraction to PCR in clinical settings.

| S-EPMC7724985 | biostudies-literature

Functional Severe Acute Respiratory Syndrome Coronavirus 2 Virus-Like Particles From Insect Cells

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a major epidemic threat since the beginning of 2020. Efforts to combat the virus and the associated coronavirus disease 2019 (COVID-19) disease are being undertaken worldwide. To facilitate the research on the virus itself, a number of surrogate systems have been developed. Here, we report the efficient production of SARS-CoV-2 virus-like particles (VLPs) in insect cells. Contrary to widely used pseudovirus particles, where only one coronaviral protein is displayed within a heterologous scaffold, developed VLPs are structurally similar to the native virus and allow for more throughput studies on the biology of the infection. On the other hand, being devoid of the viral genome, VLPs are unable to replicate and thus safe to work with. Importantly, this is the first report showing that SARS-CoV-2 VLPs can be efficiently produced in insect cells and purified using scalable affinity chromatography.

| S-EPMC8565087 | biostudies-literature

Ramping Up Antimicrobial Peptides Against Severe Acute Respiratory Syndrome Coronavirus-2.

Project description:Human-derived antimicrobial peptides (AMPs), such as defensins and cathelicidin LL-37, are members of the innate immune system and play a crucial role in early pulmonary defense against viruses. These AMPs achieve viral inhibition through a variety of mechanisms including, but not limited to, direct binding to virions, binding to and modulating host cell-surface receptors, blocking viral replication, and aggregation of viral particles and indirectly by functioning as chemokines to enhance or curb adaptive immune responses. Given the fact that we are in a pandemic of unprecedented severity and the urgent need for therapeutic options to combat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), naturally expressed AMPs and their derivatives have the potential to combat coronavirus disease 2019 (COVID-19) and impede viral infectivity in various ways. Provided the fact that development of effective treatments is an urgent public health priority, AMPs and their derivatives are being explored as potential prophylactic and therapeutic candidates. Additionally, cell-based platforms such as human mesenchymal stem cell (hMSC) therapy are showing success in saving the lives of severely ill patients infected with SARS-CoV-2. This could be partially due to AMPs released from hMSCs that also act as immunological rheostats to modulate the host inflammatory response. This review highlights the utilization of AMPs in strategies that could be implemented as novel therapeutics, either alone or in combination with other platforms, to treat CoV-2-infected individuals.

| S-EPMC8255374 | biostudies-literature

Structural basis for potent cross-neutralizing human monoclonal antibody protection against lethal human and zoonotic severe acute respiratory syndrome coronavirus challenge.

Project description:Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002, and detailed phylogenetic and epidemiological analyses have suggested that it originated from animals. The spike (S) glycoprotein has been identified as a major component of protective immunity, and 23 different amino acid changes were noted during the expanding epidemic. Using a panel of SARS-CoV recombinants bearing the S glycoproteins from isolates representing the zoonotic and human early, middle, and late phases of the epidemic, we identified 23 monoclonal antibodies (MAbs) with neutralizing activity against one or multiple SARS-CoV spike variants and determined the presence of at least six distinct neutralizing profiles in the SARS-CoV S glycoprotein. Four of these MAbs showed cross-neutralizing activity against all human and zoonotic S variants in vitro, and at least three of these were mapped in distinct epitopes using escape mutants, structure analyses, and competition assays. These three MAbs (S109.8, S227.14, and S230.15) were tested for use in passive vaccination studies using lethal SARS-CoV challenge models for young and senescent mice with four different homologous and heterologous SARS-CoV S variants. Both S227.14 and S230.15 completely protected young and old mice from weight loss and virus replication in the lungs for all viruses tested, while S109.8 completely protected mice from weight loss and clinical signs in the presence of viral titers. We conclude that a single human MAb can confer broad protection against lethal challenge with multiple zoonotic and human SARS-CoV isolates, and we identify a robust cocktail formulation that targets distinct epitopes and minimizes the likely generation of escape mutants.

| S-EPMC2268459 | biostudies-literature

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