scholarly journals Characterization of Two Neutralizing Antibodies against Rift Valley Fever Virus Gn Protein

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 259
Author(s):  
Meng Hao ◽  
Guanying Zhang ◽  
Shengnan Zhang ◽  
Zhengshan Chen ◽  
Xiangyang Chi ◽  
...  
Keyword(s):  
Rift Valley ◽  
Neutralizing Antibodies ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Severe Disease ◽  
Fever Virus ◽  
Host Cells ◽  
Valley Fever ◽  
Endosomal Membranes ◽  
Domain Iii

The Rift Valley fever virus (RVFV) is an arthropod-borne virus that can not only cause severe disease in domestic animals but also in humans. However, the licensed vaccines or available therapeutics for humans do not exist. Here, we report two Gn-specific neutralizing antibodies (NAbs), isolated from a rhesus monkey immunized with recombinant human adenoviruses type 4 expressing Rift Valley fever virus Gn and Gc protein (rHAdV4-GnGcopt). The two NAbs were both able to protect host cells from RVFV infection. The interactions between NAbs and Gn were then characterized to demonstrate that these two NAbs might preclude RVFV glycoprotein rearrangement, hindering the exposure of fusion loops in Gc to endosomal membranes after the virus invades the host cell. The target region for the two NAbs is located in the Gn domain III, implying that Gn is a desired target for developing vaccines and neutralizing antibodies against RVFV.

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 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 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 Rift Valley Fever Virus Strain MP-12 Enters Mammalian Host Cells via Caveola-Mediated Endocytosis

2012 ◽  
Vol 86 (23) ◽  
pp. 12954-12970 ◽  
Author(s):  
B. Harmon ◽  
B. R. Schudel ◽  
D. Maar ◽  
C. Kozina ◽  
T. Ikegami ◽  
...  
Keyword(s):  
Virus Strain ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Host Cells ◽  
Mammalian Host ◽  
Valley Fever

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 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 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.

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