Validation of an IgM antibody capture ELISA based on a recombinant nucleoprotein for identification of domestic ruminants infected with Rift Valley fever virus

Williams, R. B. G.; Ellis, Charlotte; Smith, S J; Potgieter, Christiaan; Wallace, David B.; Mareledwane, Vuyokazi Epipodia; Majiwa, Phelix A.O.

doi:10.1016/j.jviromet.2011.07.011

Cited by 44 publications

(47 citation statements)

References 30 publications

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“…The detection of neutralising antibodies starting at DPI 5 reported here has been similarly observed in natural and experimental infections in other animal models and humans [2], [15]–[17]. Neutralising antibodies are believed to be crucial for the early protection against RVFV [2].…”

Section: Discussionsupporting

confidence: 74%

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Innate Immune Response to Rift Valley Fever Virus in Goats

et al. 2012

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Rift Valley fever (RVF), a re-emerging mosquito-borne disease of ruminants and man, was endemic in Africa but spread to Saudi Arabia and Yemen, meaning it could spread even further. Little is known about innate and cell-mediated immunity to RVF virus (RVFV) in ruminants, which is knowledge required for adequate vaccine trials. We therefore studied these aspects in experimentally infected goats. We also compared RVFV grown in an insect cell-line and that grown in a mammalian cell-line for differences in the course of infection. Goats developed viremia one day post infection (DPI), which lasted three to four days and some goats had transient fever coinciding with peak viremia. Up to 4% of peripheral blood mononuclear cells (PBMCs) were positive for RVFV. Monocytes and dendritic cells in PBMCs declined possibly from being directly infected with virus as suggested by in vitro exposure. Infected goats produced serum IFN-γ, IL-12 and other proinflammatory cytokines but not IFN-α. Despite the lack of IFN-α, innate immunity via the IL-12 to IFN-γ circuit possibly contributed to early protection against RVFV since neutralising antibodies were detected after viremia had cleared. The course of infection with insect cell-derived RVFV (IN-RVFV) appeared to be different from mammalian cell-derived RVFV (MAM-RVFV), with the former attaining peak viremia faster, inducing fever and profoundly affecting specific immune cell subpopulations. This indicated possible differences in infections of ruminants acquired from mosquito bites relative to those due to contact with infectious material from other animals. These differences need to be considered when testing RVF vaccines in laboratory settings.

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Section: Discussionsupporting

confidence: 74%

“…However, RVFV NSs protein inhibits IFN-α and IFN-β production/induction, thereby enabling early replication and viremia [12]–[14]. Anti-RVFV antibodies are detectable 4 to 8 days following infection [15]–[17]. Neutralising antibodies are believed to be crucial for the protection of infected animals [2], [11].…”

Section: Introductionmentioning

confidence: 99%

Innate Immune Response to Rift Valley Fever Virus in Goats

et al. 2012

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“…Unfortunately to date, none of the RVFV ELISAs are FDA approved. The nucleotide sequence of the NP gene is highly conserved among different isolates, and antibodies against NP are detected early on in infection (Williams et al, 2011). Therefore, it is commonly used in antigen-capture ELISAs to detect RVFV, and in the last decade, highly sensitive and specific ELISAs for the detection of RVFV NP have been developed (Paweska et al, 2003a(Paweska et al, , b, 2005a(Paweska et al, , b, 2008Fafetine et al, 2007;Jansen van Vuren et al, 2007;Jansen van Vuren & Paweska, 2009;Pepin et al, 2010).…”

Section: Nanotrap Particles Can Capture Viral Antigensmentioning

confidence: 99%

The use of Nanotrap particles for biodefense and emerging infectious disease diagnostics

et al. 2014

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Detection of early infectious disease may be challenging due to the low copy number of organisms present. To overcome this limitation and rapidly measure low concentrations of the pathogen, we developed a novel technology: Nanotrap particles, which are designed to capture, concentrate, and protect biomarkers from complex biofluids. Nanotrap particles are thermoresponsive hydrogels that are capable of antigen capture through the coupling of affinity baits to the particles. Here, we describe recent findings demonstrating that Nanotrap particles are able to capture live infectious virus, viral RNA, and viral proteins. Capture is possible even in complex mixtures such as serum and allows the concentration and protection of these analytes, providing increased performance of downstream assays. The Nanotrap particles are a versatile sample preparation technology that has far reaching implications for biomarker discovery and diagnostic assays.

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“…It also plays an essential role in several steps within the viral replication cycle [72]. It is the most abundant viral component of the virion [28] and has been shown to be highly conserved among RVFV isolates sequenced so far [71]. Because high serum titers of N-specific IgM antibodies are engendered early post infection in both human and animal hosts, N has been a favorite antigen choice for diagnostic assays [25], [26], [73], [74].…”

Section: Discussionmentioning

confidence: 99%

“…The RVFV N protein elicits potent IgM and IgG responses that arise early after infection in humans and animals [25]–[28]. Of interest, N-subunit alone vaccines delivered as a recombinant protein [24], [29], [30] or a DNA vaccine [31]–[34] have been shown by independent laboratories to confer protection in the absence of detectable neutralizing antibodies (Abs) [29], [31], [34].…”

Section: Introductionmentioning

confidence: 99%

The Nucleocapsid Protein of Rift Valley Fever Virus Is a Potent Human CD8+ T Cell Antigen and Elicits Memory Responses

Watts

Costanzo

et al. 2013

PLoS ONE

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There is no licensed human vaccine currently available for Rift Valley Fever Virus (RVFV), a Category A high priority pathogen and a serious zoonotic threat. While neutralizing antibodies targeting the viral glycoproteins are protective, they appear late in the course of infection, and may not be induced in time to prevent a natural or bioterrorism-induced outbreak. Here we examined the immunogenicity of RVFV nucleocapsid (N) protein as a CD8+ T cell antigen with the potential for inducing rapid protection after vaccination. HLA-A*0201 (A2)-restricted epitopic determinants were identified with N-specific CD8+ T cells from eight healthy donors that were primed with dendritic cells transduced to express N, and subsequently expanded in vitro by weekly re-stimulations with monocytes pulsed with 59 15mer overlapping peptides (OLPs) across N. Two immunodominant epitopes, VT9 (VLSEWLPVT, N121–129) and IL9 (ILDAHSLYL, N165–173), were defined. VT9- and IL9-specific CD8+ T cells identified by tetramer staining were cytotoxic and polyfunctional, characteristics deemed important for viral control in vivo. These peptides induced specific CD8+ T cell responses in A2-transgenic mice, and more importantly, potent N-specific CD8+ T cell reactivities, including VT9- and IL9-specific ones, were mounted by mice after a booster vaccination with the live attenuated RVF MP-12. Our data suggest that the RVFV N protein is a potent human T cell immunogen capable of eliciting broad, immunodominant CD8+ T cell responses that are potentially protective. Understanding the immune responses to the nucleocapsid is central to the design of an effective RVFV vaccine irrespective of whether this viral protein is effective as a stand-alone immunogen or only in combination with other RVFV antigens.

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Validation of an IgM antibody capture ELISA based on a recombinant nucleoprotein for identification of domestic ruminants infected with Rift Valley fever virus

Cited by 44 publications

References 30 publications

Innate Immune Response to Rift Valley Fever Virus in Goats

Innate Immune Response to Rift Valley Fever Virus in Goats

The use of Nanotrap particles for biodefense and emerging infectious disease diagnostics

The Nucleocapsid Protein of Rift Valley Fever Virus Is a Potent Human CD8+ T Cell Antigen and Elicits Memory Responses

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