scholarly journals An alphavirus replicon-derived candidate vaccine against Rift Valley fever virus

2009 ◽  
Vol 137 (9) ◽  
pp. 1309-1318 ◽  
Author(s):  
M. T. HEISE ◽  
A. WHITMORE ◽  
J. THOMPSON ◽  
M. PARSONS ◽  
A. A. GROBBELAAR ◽  
...  
Keyword(s):  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Fluorescent Antibody ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Fever Virus ◽  
Antibody Responses ◽  
Valley Fever

SUMMARYRift Valley fever virus (RVFV) is a mosquito-transmitted bunyavirus (genusPhlebovirus) associated with severe disease in livestock and fatal encephalitis or haemorrhagic fever in a proportion of infected humans. Although live attenuated and inactivated vaccines have been used in livestock, and on a limited scale in humans, there is a need for improved anti-RVFV vaccines. Towards this goal, Sindbis virus replicon vectors expressing the RVFV Gn and Gc glycoproteins, as well as the non-structural nsM protein, were constructed and evaluated for their ability to induce protective immune responses against RVFV. These replicon vectors were shown to produce the RVFV glycoproteins to high levelsin vitroand to induce systemic anti-RVFV antibody responses in immunized mice, as determined by RVFV-specific ELISA, fluorescent antibody tests, and demonstration of a neutralizing antibody response. Replicon vaccination also provided 100% protection against lethal RVFV challenge by either the intraperitoneal or intranasal route. Furthermore, preliminary results indicate that the replicon vectors elicit RVFV-specific neutralizing antibody responses in vaccinated sheep. These results suggest that alphavirus-based replicon vectors can induce protective immunity against RVFV, and that this approach merits further investigation into its potential utility as a RVFV vaccine.

scholarly journals Inhibition of Rift Valley Fever Virus Replication and Perturbation of Nucleocapsid-RNA Interactions by Suramin

2014 ◽  
Vol 58 (12) ◽  
pp. 7405-7415 ◽  
Author(s):  
Mary Ellenbecker ◽  
Jean-Marc Lanchy ◽  
J. Stephen Lodmell
Keyword(s):  
Rift Valley ◽  
Rift Valley Fever ◽  
Rna Binding ◽  
Therapeutic Potential ◽  
Rift Valley Fever Virus ◽  
Severe Disease ◽  
Fever Virus ◽  
Valley Fever ◽  
Ribonucleoprotein Complexes

ABSTRACTRift Valley fever virus (RVFV) is an emerging infectious pathogen that causes severe disease in humans and livestock and has the potential for global spread. There are currently no proven safe and effective treatment options for RVFV infection. Inhibition of RNA binding to RVFV nucleocapsid protein (N) represents an attractive antiviral therapeutic strategy because several essential steps in the RVFV replication cycle involve N binding to viral RNA. In this study, we demonstrate the therapeutic potential of the drug suramin by showing that it functions well as an inhibitor of RVFV replication at multiple stages in human cell culture. Suramin has been used previously to treat trypanosomiasis in Africa. We characterize the dynamic and cooperative nature of N-RNA binding interactions and the dissociation of high-molecular-mass ribonucleoprotein complexes using suramin, which we previously identified as an N-RNA binding inhibitor in a high-throughput screen. Finally, we elucidate the molecular mechanism used by suraminin vitroto disrupt both specific and nonspecific binding events important for ribonucleoprotein formation.

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 Preliminary Evaluation of a Bunyavirus Vector for Cancer Immunotherapy

2015 ◽  
Vol 89 (17) ◽  
pp. 9124-9127 ◽  
Author(s):  
N. Oreshkova ◽  
L. Spel ◽  
R. P. M. Vloet ◽  
P. J. Wichgers Schreur ◽  
R. J. M. Moormann ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Preliminary Evaluation ◽  
Valley Fever ◽  
Human Dendritic Cells

Replicon particles of Rift Valley fever virus, referred to as nonspreading Rift Valley fever virus (NSR), are intrinsically safe and highly immunogenic. Here, we demonstrate that NSR-infected human dendritic cells can activate CD8+T cellsin vitroand that prophylactic and therapeutic vaccinations of mice with NSR encoding a tumor-associated CD8 peptide can control the outgrowth of lymphoma cellsin vivo. These results suggest that the NSR system holds promise for cancer immunotherapy.

scholarly journals Alterations in the host transcriptome in vitro following Rift Valley fever virus infection

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Chelsea Pinkham ◽  
Bibha Dahal ◽  
Cynthia L. de la Fuente ◽  
Nicole Bracci ◽  
Brett Beitzel ◽  
...  
Keyword(s):  
Virus Infection ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Valley Fever

scholarly journals Studies on Rift Valley fever in some African murids (Rodentia: Muridae)

1978 ◽  
Vol 80 (2) ◽  
pp. 183-196 ◽  
Author(s):  
R. Swanepoel ◽  
N. K. Blackburn ◽  
S. Efstratiou ◽  
J. B. Condy
Keyword(s):  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Haemagglutination Inhibition ◽  
Neutralizing Antibody ◽  
Fever Virus ◽  
Inhibition Activity ◽  
Valley Fever ◽  
Rhabdomys Pumilio

SUMMARYBrains, spleens and livers of 2212 murids, 27 shrews and 7 dormice, trapped at 7 sites in Rhodesia, were tested in 277 pools for the presence of Rift Valley Fever virus. There were no isolations of Rift Valley Fever, but 69 isolations of an unidentified virus were obtained. Sixteen out of 867 sera had low-titre haemagglutination-inhibition activity against Rift Valley Fever antigen, but only one out of 1260 sera had neutralizing antibody. The evidence suggests that murids fail to encounter infection in nature and are unlikely to play a role in circulation and dissemination of Rift Valley Fever virus. Four out of seven widely distributed species of murid, Rhabdomys pumilio, Saccostomys campestris, Aethomys chrysophilus and Lemniscomys griselda, were shown to be capable of circulating amounts of virus likely to be infective for mosquitoes.

Correlation Between Rift Valley Fever Virus (RVFV) Neutralizing Antibody Titers in Vaccinated Sheep and Effective Dose 50 (ED50) in Vaccinated Mice

2020 ◽  
Vol 15 (03) ◽  
pp. 01-04
Author(s):  
Heba A. Khafagy ◽  
Heba MG Abdel Aziz ◽  
Amal AM ◽  
Barghooth WM ◽  
Nermeen G Shafik
Keyword(s):  
Effective Dose ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Health Hazard ◽  
Neutralizing Antibody ◽  
Fever Virus ◽  
In Vitro Test ◽  
Valley Fever ◽  
Antibody Titers

Rift valley fever is an arthropod-born, multispecies zoonotic viral disease. Control of RVF disease depends mainly on vector control and vaccination of susceptible animals. The present work aims to detect the correlation between Rift Valley Fever Virus (RVFV) neutralizing antibody titers in vaccinated sheep using Serum Neutralization test as in vitro test and effective dose fifty in vaccinated mice as in vivo potency test and determine if they can be alternative to each other. In this work,17 inactivated RVFV vaccine batches were evaluated, applying SNT for serum samples of vaccinated sheep and ED50 in vaccinated mice. The two models of tests showed compatible results, where the same 14 vaccine batches showed satisfactory results [(SNT >1.5) and (ED50 less than 0.02)], while the other three batches revealed unsatisfactory results in both two tests. Statistical analysis of results using Wilcoxon’s test was (0.0001), indicating a significant correlation between the tests so it could be recommended to depend on SNT instead of mice inoculation in the evaluation of RVF vaccine to reduce the numbers of animals being used and to avoid the possible public health hazard.

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