scholarly journals Evaluation of the Efficacy, Potential for Vector Transmission, and Duration of Immunity of MP-12, an Attenuated Rift Valley Fever Virus Vaccine Candidate, in Sheep

2015 ◽  
Vol 22 (8) ◽  
pp. 930-937 ◽  
Author(s):  
Myrna M. Miller ◽  
Kristine E. Bennett ◽  
Barbara S. Drolet ◽  
Robbin Lindsay ◽  
James O. Mecham ◽  
...  
Keyword(s):  
Rift Valley ◽  
Neutralizing Antibodies ◽  
Rift Valley Fever ◽  
Nonstructural Protein ◽  
Rift Valley Fever Virus ◽  
Clinical Signs ◽  
Fever Virus ◽  
Vector Transmission ◽  
Valley Fever ◽  
Virulent Challenge

ABSTRACTRift Valley fever virus (RVFV) causes serious disease in ruminants and humans in Africa. In North America, there are susceptible ruminant hosts and competent mosquito vectors, yet there are no fully licensed animal vaccines for this arthropod-borne virus, should it be introduced. Studies in sheep and cattle have found the attenuated strain of RVFV, MP-12, to be both safe and efficacious based on early testing, and a 2-year conditional license for use in U.S. livestock has been issued. The purpose of this study was to further determine the vaccine's potential to infect mosquitoes, the duration of humoral immunity to 24 months postvaccination, and the ability to prevent disease and viremia from a virulent challenge. Vaccination experiments conducted in sheep found no evidence of a potential for vector transmission to 4 North American mosquito species. Neutralizing antibodies were elicited, with titers of >1:40 still present at 24 months postvaccination. Vaccinates were protected from clinical signs and detectable viremia after challenge with virulent virus, while control sheep had fever and high-titered viremia extending for 5 days. Antibodies to three viral proteins (nucleocapsid N, the N-terminal half of glycoprotein GN, and the nonstructural protein from the short segment NSs) were also detected to 24 months using competitive enzyme-linked immunosorbent assays. This study demonstrates that the MP-12 vaccine given as a single dose in sheep generates protective immunity to a virulent challenge with antibody duration of at least 2 years, with no evidence of a risk for vector transmission.

scholarly journals Vaccine Efficacy of Self-Assembled Multimeric Protein Scaffold Particles Displaying the Glycoprotein Gn Head Domain of Rift Valley Fever Virus

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 301
Author(s):  
Paul J. Wichgers Schreur ◽  
Mirriam Tacken ◽  
Benjamin Gutjahr ◽  
Markus Keller ◽  
Lucien van Keulen ◽  
...  
Keyword(s):  
Rift Valley ◽  
Neutralizing Antibodies ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Clinical Signs ◽  
Fever Virus ◽  
Valley Fever ◽  
Protein Scaffold ◽  
Head Domain ◽  
Multimeric Protein

Compared to free antigens, antigens immobilized on scaffolds, such as nanoparticles, generally show improved immunogenicity. Conventionally, antigens are conjugated to scaffolds through genetic fusion or chemical conjugation, which may result in impaired assembly or heterogeneous binding and orientation of the antigens. By combining two emerging technologies—i.e., self-assembling multimeric protein scaffold particles (MPSPs) and bacterial superglue—these shortcomings can be overcome and antigens can be bound on particles in their native conformation. In the present work, we assessed whether this technology could improve the immunogenicity of a candidate subunit vaccine against the zoonotic Rift Valley fever virus (RVFV). For this, the head domain of glycoprotein Gn, a known target of neutralizing antibodies, was coupled on various MPSPs to further assess immunogenicity and efficacy in vivo. The results showed that the Gn head domain, when bound to the lumazine synthase-based MPSP, reduced mortality in a lethal mouse model and protected lambs, the most susceptible RVFV target animals, from viremia and clinical signs after immunization. Furthermore, the same subunit coupled to two other MPSPs (Geobacillus stearothermophilus E2 or a modified KDPG Aldolase) provided full protection in lambs as well.

scholarly journals Naturally Acquired Rift Valley Fever Virus Neutralizing Antibodies Predominantly Target the Gn Glycoprotein

iScience ◽  
2020 ◽  
Vol 23 (11) ◽  
pp. 101669
Author(s):  
Daniel Wright ◽  
Elizabeth R. Allen ◽  
Madeleine H.A. Clark ◽  
John N. Gitonga ◽  
Henry K. Karanja ◽  
...  
Keyword(s):  
Rift Valley ◽  
Neutralizing Antibodies ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Valley Fever

Neutralizing antibodies against Rift Valley fever virus in wild antelope in far northern KwaZulu‐Natal, South Africa, indicate recent virus circulation

2020 ◽  
Vol 67 (3) ◽  
pp. 1356-1363
Author(s):  
Carien Van den Bergh ◽  
Estelle H. Venter ◽  
Robert Swanepoel ◽  
Cathariné C. Hanekom ◽  
Peter N. Thompson
Keyword(s):  
South Africa ◽  
Rift Valley ◽  
Neutralizing Antibodies ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Valley Fever ◽  
Kwazulu Natal

scholarly journals MVA Vectored Vaccines Encoding Rift Valley Fever Virus Glycoproteins Protect Mice against Lethal Challenge in the Absence of Neutralizing Antibody Responses

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 82 ◽  
Author(s):  
Elena López-Gil ◽  
Sandra Moreno ◽  
Javier Ortego ◽  
Belén Borrego ◽  
Gema Lorenzo ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Cellular Immunity ◽  
Rift Valley ◽  
Neutralizing Antibodies ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Valley Fever

In vitro neutralizing antibodies have been often correlated with protection against Rift Valley fever virus (RVFV) infection. We have reported previously that a single inoculation of sucrose-purified modified vaccinia Ankara (MVA) encoding RVFV glycoproteins (rMVAGnGc) was sufficient to induce a protective immune response in mice after a lethal RVFV challenge. Protection was related to the presence of glycoprotein specific CD8+ cells, with a low-level detection of in vitro neutralizing antibodies. In this work we extended those observations aimed to explore the role of humoral responses after MVA vaccination and to study the contribution of each glycoprotein antigen to the protective efficacy. Thus, we tested the efficacy and immune responses in BALB/c mice of recombinant MVA viruses expressing either glycoprotein Gn (rMVAGn) or Gc (rMVAGc). In the absence of serum neutralizing antibodies, our data strongly suggest that protection of vaccinated mice upon the RVFV challenge can be achieved by the activation of cellular responses mainly directed against Gc epitopes. The involvement of cellular immunity was stressed by the fact that protection of mice was strain dependent. Furthermore, our data suggest that the rMVA based single dose vaccination elicits suboptimal humoral immune responses against Gn antigen since disease in mice was exacerbated upon virus challenge in the presence of rMVAGnGc or rMVAGn immune serum. Thus, Gc-specific cellular immunity could be an important component in the protection after the challenge observed in BALB/c mice, contributing to the elimination of infected cells reducing morbidity and mortality and counteracting the deleterious effect of a subneutralizing antibody immune response.

scholarly journals A ΩXaV motif in the Rift Valley fever virus NSs protein is essential for degrading p62, forming nuclear filaments and virulence

2015 ◽  
Vol 112 (19) ◽  
pp. 6021-6026 ◽  
Author(s):  
Normand Cyr ◽  
Cynthia de la Fuente ◽  
Lauriane Lecoq ◽  
Irene Guendel ◽  
Philippe R. Chabot ◽  
...  
Keyword(s):  
Rift Valley ◽  
Rift Valley Fever ◽  
Excision Repair ◽  
Rna Virus ◽  
Nonstructural Protein ◽  
Rift Valley Fever Virus ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Valley Fever ◽  
Infected Cells

Rift Valley fever virus (RVFV) is a single-stranded RNA virus capable of inducing fatal hemorrhagic fever in humans. A key component of RVFV virulence is its ability to form nuclear filaments through interactions between the viral nonstructural protein NSs and the host general transcription factor TFIIH. Here, we identify an interaction between a ΩXaV motif in NSs and the p62 subunit of TFIIH. This motif in NSs is similar to ΩXaV motifs found in nucleotide excision repair (NER) factors and transcription factors known to interact with p62. Structural and biophysical studies demonstrate that NSs binds to p62 in a similar manner as these other factors. Functional studies in RVFV-infected cells show that the ΩXaV motif is required for both nuclear filament formation and degradation of p62. Consistent with the fact that the RVFV can be distinguished from otherBunyaviridae-family viruses due to its ability to form nuclear filaments in infected cells, the motif is absent in the NSs proteins of otherBunyaviridae-family viruses. Taken together, our studies demonstrate that p62 binding to NSs through the ΩXaV motif is essential for degrading p62, forming nuclear filaments and enhancing RVFV virulence. In addition, these results show how the RVFV incorporates a simple motif into the NSs protein that enables it to functionally mimic host cell proteins that bind the p62 subunit of TFIIH.

scholarly journals Genetically Modified Rabies Virus Vector-Based Rift Valley Fever Virus Vaccine is Safe and Induces Efficacious Immune Responses in Mice

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 919 ◽  
Author(s):  
Zhang ◽  
Hao ◽  
Feng ◽  
Jin ◽  
Yan ◽  
...  
Keyword(s):  
T Cells ◽  
Rabies Virus ◽  
Rift Valley ◽  
Neutralizing Antibodies ◽  
Rift Valley Fever ◽  
Memory T Cells ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Igg Antibodies ◽  
Valley Fever

Rift Valley fever virus (RVFV), which causes Rift Valley fever (RVF), is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. RVF is a World Health Organization (WHO) priority disease and, together with rabies, is a major health burden in Africa. Here, we present the development and characterization of an inactivated recombinant RVFV and rabies virus (RABV) vaccine candidate (rSRV9-eGn). Immunization with rSRV9-eGn stimulated the production of RVFV-specific IgG antibodies and induced humoral and cellular immunity in mice but did not induce the production of neutralizing antibodies. IgG1 and IgG2a were the main isotypes observed by IgG subtype detection, and IgG3 antibodies were not detected. The ratios of IgG1/IgG2a > 1 indicated a Type 2 humoral immune response. An effective vaccine is intended to establish a long-lived population of memory T cells, and mice generated memory cells among the proliferating T cell population after immunization with rSRV9-eGn, with effector memory T cells (TEM) as the major population. Due to the lack of prophylactic treatment experiments, it is impossible to predict whether this vaccine can protect animals from RVFV infection with only high titres of anti-RVFV IgG antibodies and no neutralizing antibodies induced, and thus, protection confirmation needs further verification. However, this RVFV vaccine designed with RABV as the vector provides ideas for the development of vaccines that prevent RVFV and RABV infections.

scholarly journals Protection of Sheep against Rift Valley Fever Virus and Sheep Poxvirus with a Recombinant Capripoxvirus Vaccine

2010 ◽  
Vol 17 (12) ◽  
pp. 1842-1849 ◽  
Author(s):  
Reuben K. Soi ◽  
Fred R. Rurangirwa ◽  
Travis C. McGuire ◽  
Paul M. Rwambo ◽  
James C. DeMartini ◽  
...  
Keyword(s):  
Rift Valley ◽  
Neutralizing Antibodies ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Viral Disease ◽  
Fever Virus ◽  
Recombinant Vaccines ◽  
Valley Fever ◽  
Genes Encoding ◽  
Correct Size

ABSTRACT Rift Valley fever (RVF) is an epizootic viral disease of sheep that can be transmitted from sheep to humans, particularly by contact with aborted fetuses. A capripoxvirus (CPV) recombinant virus (rKS1/RVFV) was developed, which expressed the Rift Valley fever virus (RVFV) Gn and Gc glycoproteins. These expressed glycoproteins had the correct size and reacted with monoclonal antibodies (MAb) to native glycoproteins. Mice vaccinated with rKS1/RVFV were protected against RVFV challenge. Sheep vaccinated with rKS1/RVFV twice developed neutralizing antibodies and were significantly protected against RVFV and sheep poxvirus challenge. These findings further document the value of CPV recombinants as ruminant vaccine vectors and support the inclusion of RVFV genes encoding glycoproteins in multivalent recombinant vaccines to be used where RVF occurs.

scholarly journals Genetic Evidence for an Interferon-Antagonistic Function of Rift Valley Fever Virus Nonstructural Protein NSs

2001 ◽  
Vol 75 (3) ◽  
pp. 1371-1377 ◽  
Author(s):  
Michèle Bouloy ◽  
Christian Janzen ◽  
Pierre Vialat ◽  
Huot Khun ◽  
Jovan Pavlovic ◽  
...  
Keyword(s):  
Rift Valley ◽  
Rift Valley Fever ◽  
Nonstructural Protein ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Sub Saharan Africa ◽  
Wild Type ◽  
Valley Fever ◽  
Viral Virulence ◽  
Deficient Mice

ABSTRACT Rift Valley fever virus (RVFV), a phlebovirus of the family Bunyaviridae, is a major public health threat in Egypt and sub-Saharan Africa. The viral and host cellular factors that contribute to RVFV virulence and pathogenicity are still poorly understood. All pathogenic RVFV strains direct the synthesis of a nonstructural phosphoprotein (NSs) that is encoded by the smallest (S) segment of the tripartite genome and has an undefined accessory function. In this report, we show that MP12 and clone 13, two attenuated RVFV strains with mutations in the NSs gene, were highly virulent in IFNAR−/− mice lacking the alpha/beta interferon (IFN-α/β) receptor but remained attenuated in IFN-γ receptor-deficient mice. Both attenuated strains proved to be excellent inducers of early IFN-α/β production. In contrast, the virulent strain ZH548 failed to induce detectable amounts of IFN-α/β and replicated extensively in both IFN-competent and IFN-deficient mice. Clone 13 has a defective NSs gene with a large in-frame deletion. This defect in the NSs gene results in expression of a truncated protein which is rapidly degraded. To investigate whether the presence of the wild-type NSs gene correlated with inhibition of IFN-α/β production, we infected susceptible IFNAR−/− mice with S gene reassortant viruses. When the S segment of ZH548 was replaced by that of clone 13, the resulting reassortants became strong IFN inducers. When the defective S segment of clone 13 was exchanged with the wild-type S segment of ZH548, the reassortant virus lost the capacity to stimulate IFN-α/β production. These results demonstrate that the ability of RVFV to inhibit IFN-α/β production correlates with viral virulence and suggest that the accessory protein NSs is an IFN antagonist.

scholarly journals Rift Valley fever virus: a new avenue of research on the biological functions of amyloids?

2021 ◽  
Author(s):  
Ke Peng ◽  
Pierre-Yves Lozach
Keyword(s):  
Rift Valley ◽  
Rift Valley Fever ◽  
Biological Function ◽  
Nonstructural Protein ◽  
Rift Valley Fever Virus ◽  
Febrile Illness ◽  
Fever Virus ◽  
Biological Functions ◽  
Valley Fever ◽  
Great Rift Valley

Rift Valley fever is a mosquito-borne viral zoonosis that was first discovered in the Great Rift Valley, Kenya, in 1930. Rift Valley fever virus (RVFV) primarily infects domestic animals and humans, with clinical outcomes ranging from self-limiting febrile illness to acute hepatitis and encephalitis. The virus left Africa a few decades ago, and there is a risk of introduction into southern Europe and Asia. From this perspective, we introduce RVFV and focus on the capacity of its virulence factor, the nonstructural protein NSs, to form amyloid-like fibrils. Here, we discuss the implications for the NSs biological function, the ability of RVFV to evade innate immunity, and RVFV virulence and neurotoxicity.

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