Pleomorphic, Enveloped, Virus-Like Particles Associated with Gastrointestinal Illness in Neonates

Analysis of Hepatitis C virus (HCV) assembly and packaging, and the study of virus-cell interactions, have been impeded by the lack of a robust cell culture system and a viable small animal model. Recently, an alternative approach utilizing recombinant gene technology has been implemented. We describe a system in which specific HCV genes are cloned into a baculovirus to form a recombinant baculovirus expression vector that produces HCV proteins that self-assemble into enveloped virus-like particles (VLP). Four HCV structural genes were cloned into the baculovirus expression vector under the control of the polyhedrin promoter, and were then recombined with baculovirus DNA. A baculovirus with no HCV insert served as a negative control (wild-type). Ovary cells (Spodoptera frugiperda) were infected with either the recombinant or wild type baculovirus. Five-days post-infection, a group of cells were harvested, fixed in McDowell-Trumps solution, and routinely prepared for transmission electron microscopy (TEM).

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Displaying Tetra-Membrane Spanning Claudins on Enveloped Virus-Like Particles for Cancer Immunotherapy

Biotechnology Journal ◽

10.1002/biot.201700345 ◽

2017 ◽

Vol 13 (3) ◽

pp. 1700345 ◽

Cited By ~ 4

Author(s):

Irene C. Schneider ◽

Jessica Hartmann ◽

Gundula Braun ◽

Jörn Stitz ◽

Thorsten Klamp ◽

...

Keyword(s):

Cancer Immunotherapy ◽

Virus Like Particles ◽

Enveloped Virus ◽

Membrane Spanning

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Antigenicity and immunogenicity of unique prefusion-mimic F proteins presented on enveloped virus-like particles

Vaccine ◽

10.1016/j.vaccine.2019.09.041 ◽

2019 ◽

Vol 37 (44) ◽

pp. 6656-6664

Author(s):

Young-Man Kwon ◽

Youri Lee ◽

Ki Hye Kim ◽

Yu Jin Jung ◽

Zhuo Li ◽

...

Keyword(s):

Virus Like Particles ◽

Enveloped Virus

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Polymer-grafted chromatography media for the purification of enveloped virus-like particles, exemplified with HIV-1 gag VLP

Vaccine ◽

10.1016/j.vaccine.2019.07.001 ◽

2019 ◽

Vol 37 (47) ◽

pp. 7070-7080 ◽

Cited By ~ 5

Author(s):

Patricia Pereira Aguilar ◽

Tobias Amadeus Schneider ◽

Viktoria Wetter ◽

Daniel Maresch ◽

Wai Li Ling ◽

...

Keyword(s):

Virus Like Particles ◽

Enveloped Virus ◽

Hiv 1

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cGAMP loading enhances the immunogenicity of VLP vaccines

10.1101/2020.01.03.893586 ◽

2020 ◽

Cited By ~ 1

Author(s):

Lise Chauveau ◽

Anne Bridgeman ◽

Tiong Kit Tan ◽

Ryan Beveridge ◽

Joe Frost ◽

...

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Viral Vectors ◽

Serum Antibody ◽

Gag Protein ◽

Virus Like Particles ◽

Virus Challenge ◽

Enveloped Virus ◽

Viral Vaccine

AbstractCyclic GMP-AMP (cGAMP) is an immunostimulatory second messenger produced by cGAS that activates STING. Soluble cGAMP acts as an adjuvant when administered with antigens. cGAMP is also incorporated into enveloped virus particles during budding. We hypothesised that inclusion of the adjuvant cGAMP within viral vaccine vectors would promote adaptive immunity against vector antigens. We immunised mice with virus-like particles (VLPs) containing the HIV-1 Gag protein and VSV-G. Inclusion of cGAMP within these VLPs augmented splenic VLP-specific CD4 and CD8 T cell responses. It also increased VLP- and VSV-G-specific serum antibody titres and enhanced in vitro virus neutralisation. The superior antibody response was accompanied by increased numbers of T follicular helper cells in draining lymph nodes. Vaccination with cGAMP-loaded VLPs containing haemagglutinin induced high titres of influenza A virus neutralising antibodies and conferred protection following subsequent influenza A virus challenge. Together, these results show that incorporating cGAMP into VLPs enhances their immunogenicity, making cGAMP-VLPs an attractive platform for novel vaccination strategies.Short summarycGAMP is an innate immune signalling molecule that can be transmitted between cells by inclusion in enveloped virions. This study demonstrates enhanced immunogenicity of HIV-derived virus-like particles containing cGAMP. Viral vectors loaded with cGAMP may thus be potent vaccines.

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Generating enveloped virus-like particles with in vitro assembled cores

Virology ◽

10.1016/j.virol.2011.02.001 ◽

2011 ◽

Vol 413 (2) ◽

pp. 153-160 ◽

Cited By ~ 21

Author(s):

Fan Cheng ◽

Suchetana Mukhopadhyay

Keyword(s):

Virus Like Particles ◽

Enveloped Virus

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ENVELOPED VIRUS-LIKE PARTICLES (eVLPs) EXPRESSING MODIFIED FORMS OF ZIKA VIRUS PROTEINS E AND NS1 PROTECT MICE FROM ZIKA VIRUS INFECTION

10.1101/666966 ◽

2019 ◽

Author(s):

Anne-Catherine Fluckiger ◽

Jasminka Bozic ◽

Abebaw Diress ◽

Barthelemy Ontsouka ◽

Tanvir Ahmed ◽

...

Keyword(s):

T Cell ◽

Virus Infection ◽

Zika Virus ◽

Neutralizing Antibody ◽

T Cell Response ◽

Bivalent Vaccine ◽

Virus Like Particles ◽

Enveloped Virus ◽

Zika Virus Infection ◽

Virus Proteins

AbstractWhile Zika virus (ZIKV) infection induces mild disease in the majority of cases, it has been identified as responsible for microcephaly and severe neurological disorders in recent 2015-2016 outbreaks in South America and the Caribbean. Since then, several prophylactic vaccine strategies have been studied. Here, we describe the development of a ZIKV candidate vaccine consisting of bivalent enveloped virus-like particles (eVLPs) expressing a modified form of E and truncated NS1 (EG/NS1) proteins. In EG/NS1, the E transmembrane/cytoplasmic tail has been replaced with those domains from the VSV G protein and a β-domain of NS1 was fused in-frame to Gag from Moloney murine leukemia virus (MLV). Immunization of BALB/C mice demonstrated that bivalent EG/NS1 and monovalent EG eVLPs induced comparable levels of antibody (Ab) titers but that EG/NS1 induced much higher neutralizing activity, comparable to naturally acquired anti-ZIKV immunity. In contrast, monovalent NS1 eVLPs did not induce a significant anti-NS1 Ab response but promoted strong T cell immunity that was also elicited with EG/NS1 eVLPs. ZIKV challenge studies in C57BL/6-IFNαR−/−mice demonstrated that EG/NS1 eVLPs conferred 100% protection against clinical disease after ZIKV challenge compared to 80% protection after EG eVLP vaccination, with protection against challenge correlating with neutralizing antibody titers and overt signs of infection.Author SummaryZika virus has caused rapidly spreading epidemics with potentially severe neurological symptoms including microcephaly in new born babies. Rapid progress has been made with several candidate vaccines under clinical evaluation but no vaccine or treatment is yet available. In this context, we have produced and tested recombinant virus-like particles that incorporate one or two Zika virus proteins, E and NS1 that have been modified for optimal efficacy. Our immunogenicity studies in mice showed a synergistic effect of both proteins in the bivalent vaccine. NS1 induced a strong T cell response enhancing the neutralizing antibody production induced by the E protein. In challenge experiments, the bivalent vaccine protected 100% of mice from clinical signs of Zika virus infection. These products could be further used to explore Zika virus correlates of protection and evaluated as vaccine candidates.

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