Human Antibody Neutralizes Severe Fever with Thrombocytopenia Syndrome Virus, an Emerging Hemorrhagic Fever Virus

Guo, Xiling; Zhang, Li; Zhang, Wenshuai; Cheng, Ying; Zeng, Xianying; Li, Xian; Qi, Xian; Qiu, Jin; Xiao, Zhengguo; Huang, Mingming; Wang, Hua; Chen, Yin; Bao, Changjun; Hu, Jianli; Liang, Shuyi; Lin, Bingliang; Wu, Tao; Zhou, Minghao; Jiao, Yongjun

doi:10.1128/cvi.00222-13

Cited by 65 publications

(68 citation statements)

References 32 publications

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“…H2A12 was the major binding site of N protein for most human and mouse MAbs. Guo et al [11] confirms that a human monoclonal antibody [6,7], has shown neutralizing activity against SFTSV in vitro and might be used for high risk people in the future. Its neutralizing activity is attributed to blockage of the interactions between the Gn protein and the cellular receptor, indicating that inhibition of virus-cell attachment is its main mechanism.…”

Section: Treatmentmentioning

confidence: 84%

“…At present; there is no specific medication to treat this disease. Patients are often treated with Ribavirin, a traditional nonspecific antiviral drug, but its efficacy remains uncertain [10].There is also report says that antibodies play an important role in curing the disease [11]. Neutralizing antibodies can reduce viral load, and prevent SFTSV spreading.…”

Section: Introductionmentioning

confidence: 99%

“…Neutralizing antibodies can reduce viral load, and prevent SFTSV spreading. A human monoclonal antibody, 4-5, has been shown to have neutralizing activity against SFTSV in vitro and it might be used for high risk people in the future [11]. For now, there is no effective vaccine to prevent SFTSV infection, so people living in rural areas should pay special attention to this virus, taking some preventive measures, for example protection against tick bites, avoidance of wooded and bushy areas where ticks are abundant, especially in April or May.…”

mentioning

confidence: 99%

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A Newly Discovered Severe Fever with Thrombocytopenia Syndrome Virus and its Mechanisms in Evading Host Innate Immunity

Chen¹

2015

J Antivir Antiretrovir

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IntroductionSFTSV is a newly discovered virus that was first reported in 2009 in China [1]. It was known as Huaiyangshan virus which is a new member of the Phlebovirus genus from the Bunyaviridae family [1]. Clinically, SFTSV can cause fever, gastrointestinal symptoms, myalgia, and regional lymphadenopathy [2]. The most significant manifestations of this disease are severe fever and thrombocytopenia [3]. The disease which could be transmitted through ticks has been found in many cities in China now, and the highest numbers of reported cases were in Henan (48% of the total), Hubei (22%), and Shangdong (16%) [4]. Epidemiological study shows that 1.0%-3.8% of the examined population in hilly areas had SFTSV antibodies, which suggests that SFTSV has circulated widely in China, especially in rural areas [5]. SFTSV infection was also reported in other Asia countries such as Korea and Japan [6,7]. The mortality of SFTSV infection in China is about 2.5%-30% [8]. Most patients are farmers who come from rural areas. Many of them have reported tick bites 7-9 days before getting illness. The disease occurs mainly in April and May during the peaking season in Henan [9]. One study indicated that SFTSV could cause the asymptomatic infections via person-to-person contact with infected blood [6]. At present; there is no specific medication to treat this disease. Patients are often treated with Ribavirin, a traditional nonspecific antiviral drug, but its efficacy remains uncertain [10].There is also report says that antibodies play an important role in curing the disease [11]. Neutralizing antibodies can reduce viral load, and prevent SFTSV spreading. A human monoclonal antibody, 4-5, has been shown to have neutralizing activity against SFTSV in vitro and it might be used for high risk people in the future [11]. For now, there is no effective vaccine to prevent SFTSV infection, so people living in rural areas should pay special attention to this virus, taking some preventive measures, for example protection against tick bites, avoidance of wooded and bushy areas where ticks are abundant, especially in April or May. Repellents, such as permethrin can also be applied [12,13]. SFTSV is susceptible to acid, heat, ether, sodium deoxycholate, other common disinfectants, and ultraviolet irradiation, and can be rapidly inactivated [14][15][16][17][18][19]. . M segment encodes the Gn and Gc which mediate SFTSV entry into human and animal cell lines [16]. Most recently, it has been shown that the lectin dendritic-cellspecific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) facilitates certain Phleboviruses entry into dendritic cells via Gn/Gc mediation, and over-expression of DC-SIGN was sufficient for SFTSV Gn/Gc-mediated entry into otherwise non-susceptible cells [22]. Glycoproteins encoded by M segment are also excellent targets for neutralizing antibodies [17]. Monocytic cells (THP-1), HEF, and cervical carcinoma (Hela) cells were resistant to SFTSV Gn/Gc mediated entry, which indicating that these cells may lack the ...

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Section: Treatmentmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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A Newly Discovered Severe Fever with Thrombocytopenia Syndrome Virus and its Mechanisms in Evading Host Innate Immunity

Chen¹

2015

J Antivir Antiretrovir

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“…The majority of anti-SFTSV human and murine MAbs developed have been nucleocapsid-specific and non-neutralizing. 6,7 The exception was a hMAb recognizing a linear epitope in the ectodomain of Gn found to be capable of neutralizing SFTSV in vitro by blocking virus cell-mediated attachment. 7 The N protein has also been shown to be the immunodominant protein in other phleboviral infections including Rift Valley fever virus (RFTV) and Toscana (TOSV) viruses.…”

mentioning

confidence: 99%

“…6,7 The exception was a hMAb recognizing a linear epitope in the ectodomain of Gn found to be capable of neutralizing SFTSV in vitro by blocking virus cell-mediated attachment. 7 The N protein has also been shown to be the immunodominant protein in other phleboviral infections including Rift Valley fever virus (RFTV) and Toscana (TOSV) viruses. 8,9 It is highly conserved in bunyaviruses and is the most abundantly expressed viral protein in virus-infected cells.…”

mentioning

confidence: 99%

Development and Characterization of Monoclonal Antibodies Directed Against the Nucleoprotein of Heartland Virus

Calvert¹,

Brault²

2015

The American Society of Tropical Medicine and Hygiene

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Abstract. Heartland virus (HRTV), a phlebovirus first isolated from two Missouri farmers in 2009, has been proposed to be transmitted to humans by the bite of infected Amblyomma americanum ticks. It is closely related to severe fever with thrombocytopenia syndrome virus (SFTSV) from China, another previously unrecognized phlebovirus that has subsequently been associated with hundreds of cases of severe disease in humans. To expand diagnostic capacity to detect HRTV infections, 20 hybridoma clones secreting anti-HRTV murine monoclonal antibodies (MAbs) were developed using splenocytes from HRTV-inoculated AG129 alpha/beta and gamma interferon receptor-deficient mice. Nine of these MAbs were characterized herein for inclusion in future HRTV diagnostic assay development. All of the MAbs developed were found to be non-neutralizing and reactive to linear epitopes on HRTV nucleocapsid protein. MAb 2AF11 was found to be cross-reactive with SFTSV.Heartland virus (HRTV) is a newly identified virus member of the Phlebovirus genus in the family Bunyaviridae. It was first isolated from two hospitalized Missouri farmers in separate locations within the state in 2009. 1 HRTV has been proposed to be transmitted to humans by the bite of infected Amblyomma americanum ticks. 2 It causes severe disease characterized by fever, leukopenia, and thrombocytopenia. 1 HRTV is closely related to severe fever with thrombocytopenia virus (SFTSV), a phlebovirus causing severe disease in China and neighboring countries. 3 The average case fatality rate of SFTSV infection is between 6% and 17% with the most severe manifestations occurring in elderly individuals. 4 HRTV has a single-stranded RNA genome of negative or ambisense polarity encoded on three segments. The large (L) segment encodes the RNA-dependent-RNA polymerase, the medium (M) segment encodes a precursor of the glycoproteins Gn and Gc, and the small (S) segment encodes the nucleocapsid (N) protein and a nonstructural (Ns) protein. 5 Serological assays for the detection of HRTV are currently limited to the detection of neutralizing antibodies by plaque reduction neutralization test (PRNT). The limitation in the range of assays developed is due to the absence of suitable anti-HRTV monoclonal antibodies (MAbs). To develop diagnostic assays able to detect both recent and prior infections and to assess the disease burden of HRTV infection in the United States, anti-HRTV murine MAbs were developed and characterized. Interferon receptor-deficient AG129 mice approximately 3 weeks of age were inoculated intraperitoneally (IP) with 100 plaque-forming units (PFU) of HRTV strain MO-4. After 30 days, mice were bled and boosted with another 100 PFU of HRTV MO-4 IP. Splenocytes were harvested 4 days after the last inoculation for fusions with the mouse myeloma cell line P3X63Ag8.653 using the ClonaCell-HY

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SFTSV Gn‐Head mRNA vaccine confers efficient protection against lethal viral challenge

Kim,

Lai,

Cha

et al. 2023

Journal of Medical Virology

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Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick‐borne virus, causing thrombocytopenia and hemorrhagic fever, with a fatality rate ranging from 12% to 30%. SFTSV possesses Gn and Gc glycoproteins, which are responsible for host cell receptor attachment and membrane fusion, respectively, to infect host cells. We have previously reported a protein subunit vaccine candidate (sGn‐H‐FT) of the SFTSV soluble Gn head region (sGn‐H) fused with self‐assembling ferritin (FT) nanoparticles, displaying strong protective immunogenicity. In this study, we present messenger RNA (mRNA) vaccine candidates encoding sGn‐H or sGn‐H‐FT, both of which exhibit potent in vivo immunogenicity and protection capacity. Mice immunized with either sGn‐H or sGn‐H‐FT mRNA lipid nanoparticle (LNP) vaccine produced strong total antibodies and neutralizing antibodies (NAbs) against sGn‐H. Importantly, NAb titers remained high for an extended period. Finally, mice immunized with sGn‐H or sGn‐H‐FT mRNA LNP vaccine were fully protected from a lethal dose of SFTSV challenge, showing no fatality. These findings underscore the promise of sGn‐H and sGn‐H‐FT as vaccine antigen candidates capable of providing protective immunity against SFTSV infection.

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Human Antibody Neutralizes Severe Fever with Thrombocytopenia Syndrome Virus, an Emerging Hemorrhagic Fever Virus

Cited by 65 publications

References 32 publications

A Newly Discovered Severe Fever with Thrombocytopenia Syndrome Virus and its Mechanisms in Evading Host Innate Immunity

A Newly Discovered Severe Fever with Thrombocytopenia Syndrome Virus and its Mechanisms in Evading Host Innate Immunity

Development and Characterization of Monoclonal Antibodies Directed Against the Nucleoprotein of Heartland Virus

SFTSV Gn‐Head mRNA vaccine confers efficient protection against lethal viral challenge

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