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.

Identification and characterization of Rift Valley fever virus-specific T cells reveals a dependence on CD40/CD40L interactions for prevention of encephalitis

2021 ◽  
Author(s):  
Dominique J. Barbeau ◽  
Haley N. Cartwright ◽  
Jessica R. Harmon ◽  
Jessica R. Spengler ◽  
Christina F. Spiropoulou ◽  
...  
Keyword(s):  
T Cells ◽  
Adaptive Immunity ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Rift Valley Fever Virus ◽  
Fever Virus ◽  
Mouse Strains ◽  
Valley Fever

Rift Valley fever virus (RVFV) is an arbovirus found throughout Africa. It causes disease that is typically mild and self-limiting; however, some infected individuals experience severe manifestations, including hepatitis, encephalitis, or even death. Reports of RVFV encephalitis are notable amongst immunosuppressed individuals, suggesting a role for adaptive immunity in preventing this severe complication. This phenomenon has been modeled in C57BL/6 mice depleted of CD4 T cells prior to infection with DelNSs RVFV (RVFV containing a deletion of NSs), resulting in late-onset encephalitis accompanied by high levels of viral RNA in the brain in 30% of animals. In this study, we sought to define the specific type(s) of CD4 T cells that mediate protection from RVFV encephalitis. The viral epitopes targeted by CD4 and CD8 T cells were defined in C57BL/6 mice, and tetramers for both CD4 and CD8 T cells were generated. RVFV-specific CD8 T cells were expanded and of a cytotoxic and proliferating phenotype in the liver following infection. RVFV-specific CD4 T cells were identified in the liver and spleen following infection and phenotyped as largely Th1 or Tfh subtypes. Knock-out mice lacking various aspects of pathways important in Th1 and Tfh development and function were used to demonstrate that T-bet, CD40, CD40L, and MHCII mediated protection from RVFV encephalitis, while IFN-γ and IL-12 were dispensable. Virus-specific antibody responses correlated with protection from encephalitis in all mouse strains, suggesting that Tfh-B cell interactions modulate clinical outcome in this model. Importance: The prevention of RVFV encephalitis requires intact adaptive immunity. In this study we develop reagents to detect RVFV-specific T cells and provide evidence for Tfh cells and CD40/CD40L interactions as critical mediators of this protection.

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.

A novel indirect ELISA based on glycoprotein Gn for the detection of IgG antibodies against Rift Valley fever virus in small ruminants

2013 ◽  
Vol 95 (2) ◽  
pp. 725-730 ◽  
Author(s):  
S. Jäckel ◽  
M. Eiden ◽  
A. Balkema-Buschmann ◽  
M. Ziller ◽  
P. Jansen van Vuren ◽  
...  
Keyword(s):  
Rift Valley ◽  
Rift Valley Fever ◽  
Indirect Elisa ◽  
Rift Valley Fever Virus ◽  
Small Ruminants ◽  
Fever Virus ◽  
Igg Antibodies ◽  
Valley Fever

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.

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 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.

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