Novel suspension cell-based vaccine production systems for Rift Valley fever virus-like particles

Mandell, Robert B.; Koukuntla, Ramesh; Mogler, Laura J.K.; Carzoli, Andrea K.; Holbrook, Michael R.; Martin, Brian K.; Vahanian, Nicholas N.; Link, Charles J.; Flick, Ramon

doi:10.1016/j.jviromet.2010.07.015

Cited by 21 publications

(23 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We and others have previously reported efficient VLP production systems and VLPs comprising only the Gn and Gc proteins are highly effective vaccine candidates (20,29,31,32,35,38). Mandell et al demonstrated that including the N protein in VLPs improves vaccine efficacy (31), which could be due to stabilization of the particle and/or to partial protective efficacy mediated by the N protein alone (11).…”

Section: Discussionmentioning

confidence: 98%

Creation of a Nonspreading Rift Valley Fever Virus

Kortekaas

Oreshkova

Cobos-Jiménez

et al. 2011

J Virol

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 98%

Creation of a Nonspreading Rift Valley Fever Virus

Kortekaas

Oreshkova

Cobos-Jiménez

et al. 2011

J Virol

View full text Add to dashboard Cite

show abstract

“…Co-expression of the RVFV glycoproteins Gne and Gc in cell culture has been shown to result in the formation of VLPs (de Boer et al 2010, Mandell et al 2010b. Thus, to rule out the possibility of assembly of recombinant Gne and Gc upon mixing of the proteins into vaccine formulation, an examination by transmission electron microscopy (TEM) was performed.…”

Section: Electron Microscopymentioning

confidence: 99%

A Glycoprotein Subunit Vaccine Elicits a Strong Rift Valley Fever Virus Neutralizing Antibody Response in Sheep

Faburay

Lebedev²,

McVey³

et al. 2014

Vector-Borne and Zoonotic Diseases

View full text Add to dashboard Cite

Rift Valley fever virus (RVFV), a member of the Bunyaviridae family, is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. The recent spread of the virus beyond its traditional endemic boundaries in Africa to the Arabian Peninsula coupled with the presence of susceptible vectors in nonendemic countries has created increased interest in RVF vaccines. Subunit vaccines composed of specific virus proteins expressed in eukaryotic or prokaryotic expression systems are shown to elicit neutralizing antibodies in susceptible hosts. RVFV structural proteins, amino-terminus glycoprotein (Gn), and carboxylterminus glycoprotein (Gc), were expressed using a recombinant baculovirus expression system. The recombinant proteins were reconstituted as a GnGc subunit vaccine formulation and evaluated for immunogenicity in a target species, sheep. Six sheep were each immunized with a primary dose of 50 lg of each vaccine immunogen with the adjuvant montanide ISA25; at day 21, postvaccination, each animal received a second dose of the same vaccine. The vaccine induced a strong antibody response in all animals as determined by indirect enzyme-linked immunosorbent assay (ELISA). A plaque reduction neutralization test (PRNT 80 ) showed the primary dose of the vaccine was sufficient to elicit potentially protective virus neutralizing antibody titers ranging from 40 to 160, and the second vaccine dose boosted the titer to more than 1280. Furthermore, all animals tested positive for neutralizing antibodies at day 328 postvaccination. ELISA analysis using the recombinant nucleocapsid protein as a negative marker antigen indicated that the vaccine candidate is DIVA (differentiating infected from vaccinated animals) compatible and represents a promising vaccine platform for RVFV infection in susceptible species.

show abstract

“…However, the method should be especially useful for analysis of viruses where little is known about the antigenic determinants, or for other biodefense targets that require experiments at higher biosafety containment levels[63, 64]. Preparing a PCP-consensus from many different viral strains gives reference values for PCPs at each position, a logical starting point for experimental analysis.…”

Section: Discussionmentioning

confidence: 99%

Simplifying complex sequence information: A PCP-consensus protein binds antibodies against all four Dengue serotypes

Bowen

Lewis

et al. 2012

Vaccine

View full text Add to dashboard Cite

Designing proteins that reflect the natural variability of a pathogen is essential for developing novel vaccines and drugs. Flaviviruses, including Dengue (DENV) and West Nile (WNV), evolve rapidly and can “escape” neutralizing monoclonal antibodies by mutation. Designing antigens that represent many distinct strains is important for DENV, where infection with a strain from one of the four serotypes may lead to severe hemorrhagic disease on subsequent infection with a strain from another serotype. Here, a DENV physicochemical property (PCP)-consensus sequence was derived from 671 unique sequences from the Flavitrack database. PCP-consensus proteins for domain 3 of the envelope protein (EdomIII) were expressed from synthetic genes in E. coli. The ability of the purified consensus proteins to bind polyclonal antibodies generated in response to infection with strains from each of the four DENV serotypes was determined. The initial consensus protein bound antibodies from DENV-1-3 in ELISA and Western blot assays. This sequence was altered in 3 steps to incorporate regions of maximum variability, identified as significant changes in the PCPs, characteristic of DENV-4 strains. The final protein was recognized by antibodies against all four serotypes. Two amino acids essential for efficient binding to all DENV antibodies are part of a discontinuous epitope previously defined for a neutralizing monoclonal antibody. The PCP-consensus method can significantly reduce the number of experiments required to define a multivalent antigen, which is particularly important when dealing with pathogens that must be tested at higher biosafety levels.

show abstract

Novel suspension cell-based vaccine production systems for Rift Valley fever virus-like particles

Cited by 21 publications

References 57 publications

Creation of a Nonspreading Rift Valley Fever Virus

Creation of a Nonspreading Rift Valley Fever Virus

A Glycoprotein Subunit Vaccine Elicits a Strong Rift Valley Fever Virus Neutralizing Antibody Response in Sheep

Simplifying complex sequence information: A PCP-consensus protein binds antibodies against all four Dengue serotypes

Contact Info

Product

Resources

About