Dimming the corona: studying SARS-coronavirus-2 at reduced biocontainment level using replicons and virus-like particles DOI Creative Commons
Grace Neilsen,

Asha Maria Mathew,

J.M. Castro

et al.

mBio, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 12, 2024

The coronavirus-induced disease 19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections, has had a devastating impact on millions of lives globally, with mortality rates and catastrophic social implications. Developing tools for effective vaccine strategies platforms is essential controlling preventing the recurrence such pandemics. Moreover, molecular virology that facilitate study viral pathogens, mutations, interactions various host proteins are essential. Viral replicon- virus-like particle (VLP)-based systems excellent examples tools. This review outlines importance, advantages, disadvantages both VLP-based have been developed SARS-CoV-2 helped scientific community in dimming intensity COVID-19 pandemic.

Language: Английский

Development of Methods to Produce SARS CoV‐2 Virus‐Like Particles at Scale DOI Creative Commons
Melissa A. Edeling, Linda Earnest, Julio Carrera Montoya

et al.

Biotechnology and Bioengineering, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

ABSTRACT The devastating global toll precipitated by the SARS CoV‐2 outbreak and profound impact of vaccines in stemming that has established need for molecular platforms capable rapidly delivering effective, safe accessible medical interventions pandemic preparedness. We describe a simple, efficient adaptable process to produce virus‐like particles (VLPs) can be readily scaled manufacturing. A rapid but gentle method tangential flow filtration using 100 kDa semi‐permeable membrane concentrates buffer exchanges 0.5 L VLP containing supernatant into low salt optimal pH anion exchange chromatography. VLPs are washed, eluted under high salt, dialyzed physiological buffer, sterile filtered aliquoted storage at –80°C. Purification is completed less than 2 days. simple quality control includes Western blot coincident detection Spike, Membrane Envelope protein as proxy intact VLP, ELISA detect conformationally sensitive Spike available anti‐Spike and/or anti‐RBD antibodies, negative stain immunogold electron microscopy validate particulate, crowned VLPs. This preclinical studies serves roadmap preparation more distantly related

Language: Английский

Citations

1
Is there still hope for the prophylactic hepatitis C vaccine? A review of different approaches DOI
Piotr Rzymski, Aliyu Tijani Jibril, Laila Rahmah

et al.

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(9)

Published: Sept. 1, 2024

Abstract Despite remarkable progress in the treatment of hepatitis C virus (HCV) infection, it remains a significant global health burden, necessitating development an effective prophylactic vaccine. This review paper presents current landscape HCV vaccine candidates and approaches, including more traditional, based on inactivated virus, modern, such as subunit protein, vectored, nucleic acids (DNA mRNA) virus‐like particles. The concept is first put context viral genetic diversity adaptive responses to understanding which crucial guiding against complex virus. Because ethical dimensions are also research, development, potential deployment, we address them this paper. road safe prevent infection bumpy due variation its ability evade immune responses. cell‐culture systems allowed for production candidate, can induce cross‐neutralizing antibodies vitro , but whether could humans unknown. Subunit protein that entered clinical trials elicited HCV‐specific humoral cellular responses, though be shown they translate into prevention or progression chronic state. Such were induced by clinically tested vector‐based decreased load did not infection. These disappointments readily predicted from preclinical animal studies. platforms employing particles, DNA, mRNA provide opportunities vaccine, their has yet shown. Ensuring designed conserved epitope(s) elicits broadly neutralizing essential. Given failures developing continue supporting national strategies, funding screening programs. However, these actions likely insufficient permanently control encouraging further mobilization resources research missing element elimination public health.

Language: Английский

Citations

5
Human Nasal Epithelium Organoids for Assessing Neutralizing Antibodies to a Protective SARS-CoV-2 Virus-like Particle Vaccine DOI Creative Commons
Julio Carrera Montoya, Simon Collett, Daniel Fernandez‐Ruiz

et al.

Organoids, Journal Year: 2024, Volume and Issue: 3(1), P. 18 - 31

Published: Feb. 1, 2024

Existing mRNA COVID-19 vaccines have shown efficacy in reducing severe cases and fatalities. However, their effectiveness against infection caused by emerging SARS-CoV-2 variants has waned considerably, necessitating the development of variant vaccines. Ideally, next-generation will be capable eliciting broader more sustained immune responses to effectively counteract new variants. Additionally, vitro assays that closely represent virus neutralization humans would greatly assist analysis protective vaccine-induced antibody responses. Here, we present findings from a VLP vaccine encompassing three key structural proteins: Spike (S), Envelope (E), Membrane (M). The produced neutralizing antibodies as determined surrogate test, induced virus-specific T-cell responses: predominantly CD4+, although CD8+ T cell were detected. prominent with delivered AddaVax compared alone. adjuvanted was completely live challenge mice. Furthermore, utilized air–liquid-interface (ALI)-differentiated human nasal epithelium (HNE) an system, which authentically models neutralization. We show sera VLP-vaccinated mice neutralized infection, demonstrating potential ALI-HNE assess Nab.

Language: Английский

Citations

4
The recent advances in vaccine adjuvants DOI Creative Commons

Jiayin Xing,

Xiangxiang Zhao, Xiaotian Li

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: May 13, 2025

Vaccine adjuvants, as key components in enhancing vaccine immunogenicity, play a vital role modern vaccinology. This review systematically examines the historical evolution and mechanisms of with particular emphasis on innovative advancements aluminum-based emulsion-based nucleic acid adjuvants (e.g., CpG oligonucleotides). Specifically, aluminum enhance immune responses through particle formation/antigen adsorption, inflammatory cascade activation, T-cell stimulation. Emulsion amplify immunogenicity via antigen depot effects localized inflammation, while like oligonucleotides directly activate B cells dendritic to promote Th1-type memory generation. The article further explores prospective applications these novel combating emerging pathogens (including influenza SARS-CoV-2), particularly highlighting their significance improving potency durability. Moreover, this underscores critical importance adjuvant development next-generation design provides theoretical foundations for creating safer, effective adjuvant.

Language: Английский

Citations

0
A subunit vaccine based on P97R1, P46, P42, and P65 from Mycoplasma hyopneumoniae can induce significant immune response in piglets DOI Creative Commons

Yintao He,

Kaiyuan Xie,

Zhongmao Yuan

et al.

Frontiers in Veterinary Science, Journal Year: 2024, Volume and Issue: 11

Published: Nov. 13, 2024

Mycoplasma pneumonia (MPS), caused by hyopneumoniae (Mhp), is a chronic, airborne respiratory disease that poses significant threat to the global swine industry. The P97 and P46 proteins are major antigens of Mhp, with R1 region possessing full adhesive capability. Studies have shown main antigenic regions Mhp P42 P65 exhibit strong immunogenicity. In this study, we first linked genes encoding P97R1 form P97R1P65 gene subsequently constructed three shuttle plasmids: pFBD-P97R1P46, pFBD-P97R1P46-p65, pFBD-P65-P42. These were expressed using Bac system formulated into subunit vaccines for mouse immunization. Mouse experiments indicated P97R1P46 + P65-P42 protein combination elicited higher levels specific antibodies, IL-2, IL-4, CD8 T cells compared other vaccine groups, finding further validated in subsequent challenge protection experiments. Therefore, utilized MultiBac expression co-express P97R1P46, P65, pFastMultibacDual vector immunization piglets. piglet demonstrated prepared study could induce antibodies against inducing highest level humoral immunity. This provides valuable insights development vaccines.

Language: Английский

Citations

1
Preclinical Evaluation of a Cross-Protective ß-SARS-CoV-2 Virus-Like Particle Vaccine Adjuvanted with MF59 DOI
Linda Earnest, Daniel Fernandez‐Ruiz, Melissa A. Edeling

et al.

Published: Jan. 1, 2024

Download This Paper Open PDF in Browser Add to My Library Share: Permalink Using these links will ensure access this page indefinitely Copy URL DOI

Language: Английский

Citations

0
Preclinical evaluation of a cross-protective ß-SARS-CoV-2 virus-like particle vaccine adjuvanted with MF59 DOI Creative Commons
Joseph Torresi, Linda Earnest, Daniel Fernandez‐Ruiz

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 22, 2024

Abstract Background: The COVID-19 pandemic led to the development of many vaccines, most notably mRNA and recombinant adenoviral vaccines. Whilst vaccines proved be effective in preventing severe COVID disease, they failed prevent infection or control ongoing emergence vaccine escape variant viruses. rapid waning induced antibody responses has also necessitated frequent boosting. Methods: We report findings a ß-SARS-CoV-2 virus like particle (VLP) vaccine. ß-S13EM-SARS-CoV-2 VLPs were composed viral spike (S), membrane (M) envelope (E) proteins. produced Vero cell factories purified from culture supernatants using tangential flow filtration, diafiltration, anion exchange chromatography ultrafiltration characterised by ELISA, Western blot, electron microscopy. was formulated with Addavax MF59 tested for immunogenicity protection mice. Results: strongly reactive ELISA probing anti-S anti-ß-RBD antibodies. blot showed presence S, M E proteins, protein present as dimer. strong responses. T depletion studies confirmed that CD4+ predominated. ß-S13EM-SARS-CoV-2/Addavax completely protective mice against pulmonary beta SARS-CoV-2 virus. similarly immunogenic producing high titre beta, delta omicronBA.5 Multiplex RBD-ACE2 binding inhibition assay revealed immune sera immunised broad neutralising antibodies (NAb) Alpha, Delta, Beta, Gamma Mu variants. At highest dose 20µg, VLPs/MF59 NAb Omicron BA.1, BA.2, BA.5 XBB1.5. Conclusion: These results demonstrate VLP is offers viable alternative approach supplement current

Language: Английский

Citations

0
Dimming the corona: studying SARS-coronavirus-2 at reduced biocontainment level using replicons and virus-like particles DOI Creative Commons
Grace Neilsen,

Asha Maria Mathew,

J.M. Castro

et al.

mBio, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 12, 2024

The coronavirus-induced disease 19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections, has had a devastating impact on millions of lives globally, with mortality rates and catastrophic social implications. Developing tools for effective vaccine strategies platforms is essential controlling preventing the recurrence such pandemics. Moreover, molecular virology that facilitate study viral pathogens, mutations, interactions various host proteins are essential. Viral replicon- virus-like particle (VLP)-based systems excellent examples tools. This review outlines importance, advantages, disadvantages both VLP-based have been developed SARS-CoV-2 helped scientific community in dimming intensity COVID-19 pandemic.

Language: Английский

Citations

0