Passive Transfer of Serum Antibodies Induced by BBG2Na, a Subunit Vaccine, in the Elderly Protects SCID Mouse Lungs Against Respiratory Syncytial Virus Challenge

Plotnicky-Gilquin, Hélène; Cyblat-Chanal, Dominique; Goetsch, Liliane; Lacheny, Christine; Libon, Christine; Champion, Thierry; Beck, Alain; Pasche, Hélène; Nguyen, Thien Ngoc; Bonnefoy, Jean Yves; Bouveret-le-Cam, Nancy; Corvaı̈a, Nathalie

doi:10.1006/viro.2002.1563

Cited by 17 publications

(9 citation statements)

References 25 publications

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“…To further study the activity of 3,4-DCQAME to reduce viral load and block viral replication in vivo, we repeated the experiments using immunodeficient SCID mice, which are believed to support more robust RSV infection than immunocompetent BALB/c mice (36). At 7 d postinfection, viral F mRNA levels and titers were found to be substantial in the lung tissues of RSV-infected SCID mice ( Fig.…”

Section: In Vivo Inhibition Of Rsv Infection By 34-dcqamementioning

confidence: 99%

Small molecule inhibits respiratory syncytial virus entry and infection by blocking the interaction of the viral fusion protein with the cell membrane

Tang

Liu

et al. 2018

FASEB j.

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Antiviral drug development against respiratory syncytial virus (RSV) is urgently needed due to the public health significance of the viral infection. Here, we report the anti‐RSV activity of a small molecule, (1S,3R,4R,5R)‐3,4‐bis{[(E)‐3‐(3,4‐dihydroxyphenyl)prop‐2‐enoyl]oxy}‐l,5‐dihydroxycyclohexane‐1‐ca methyl ester (3,4‐DCQAME) or 3,4‐O‐Dicaffeoylquinic acid methyl ester, which can be isolated from several plants of traditional Chinese medicine. We showed for the first time that compound 3,4‐DCQAME potently inhibits RSV entry and infection. In vitro, 3,4‐DCQAME can interact with F(ecto), the ectodomain of RSV fusion (F) protein. In cultured cells, the compound can block the interaction of F(ecto) protein with the cellular membrane and inhibit viral fusion during RSV entry, leading to inhibition of viral gene expression and infection. In RSV‐infected mice that were treated with 3,4‐DCQAME, we observed a reduction of RSV‐induced pathologic changes and substantial inhibition of viral infection and growth in the lung tissues. Our results provide the first direct evidence of the anti‐RSV activity of 3,4‐DCQAME. Furthermore, these results suggest that 3,4‐DCQAME represents a promising lead compound for anti‐RSV therapeutic development.—Tang, W., Li, M., Liu, Y., Liang, N., Yang, Z., Zhao, Y., Wu, S., Lu, S., Li, Y., Liu, F. Small molecule inhibits respiratory syncytial virus entry and infection by blocking the interaction of the viral fusion protein with the cell membrane. FASEB J. 33, 4287–4299 (2019). http://www.fasebj.org

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Section: In Vivo Inhibition Of Rsv Infection By 34-dcqamementioning

confidence: 99%

Small molecule inhibits respiratory syncytial virus entry and infection by blocking the interaction of the viral fusion protein with the cell membrane

Tang

Liu

et al. 2018

FASEB j.

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“…This CX3C motif is highly conserved across 37 different virus strains [14]. Furthermore, this region has very low immunogenicity, even as a subunit vaccine [39]. …”

Section: Molecular Dissection Of Rsv G-proteinmentioning

confidence: 99%

“…Sera from elderly subjects vaccinated with an RSV G-protein construct were effective as a prophylactic in nude mice [39]. More recently, higher-affinity mAbs to either RSV G- or F-proteins have been shown to be even more active in these animal models than the first-generation mAb palivizumab [14,43].…”

Section: Antibody Treatment Modelsmentioning

confidence: 99%

Therapeutic targeting of respiratory syncytial virus G-protein

et al. 2010

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Respiratory syncytial virus (RSV) is a leading cause of pneumonia and bronchiolitis in infants and young children and an important pathogen of the elderly and immune suppressed. The only intervention currently available is a monoclonal antibody against the RSV fusion protein, which has shown utility as a prophylactic for high-risk premature infants, but which has not shown postinfection therapeutic efficacy in the specific RSV-infected populations studied. Thus, for the major susceptible populations, there remains a great need for effective treatment. Recent results support monoclonal antibody targeting of the RSV G-protein for therapeutic use. This objective encompasses a dual mechanism: reduction in the ability of RSV G-protein to distort the host innate immune response, and direct complement-mediated antiviral activity.

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“…Evidence indicates that the RSV F protein is important in inducing protective immunity (19,38), but studies evaluating a BBG2Na vaccine candidate in combination with different adjuvants and by different routes of administration have shown a role for G protein in protection against RSV in rodents (4,10,17,32,43,44,49,51). The structural elements of the G protein fragment in the BBG2Na vaccine candidate implicated in protective efficacy were mapped, and five different B-cell epitopes were determined, i.e., residues 145 to 159, 164 to 176, 171 to 187, 172 to 187, and 190 to 204 (44,48).…”

mentioning

confidence: 99%

Vaccination To Induce Antibodies Blocking the CX3C-CX3CR1 Interaction of Respiratory Syncytial Virus G Protein Reduces Pulmonary Inflammation and Virus Replication in Mice

Zhang

Choi

Haynes

et al. 2010

J Virol

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Respiratory syncytial virus (RSV) infection causes substantial morbidity and some deaths in the young and elderly worldwide. There is no safe and effective vaccine available, although it is possible to reduce the hospitalization rate for high-risk children by anti-RSV antibody prophylaxis. RSV has been shown to modify the immune response to infection, a feature linked in part to RSV G protein CX3C chemokine mimicry. This study determined if vaccination with G protein polypeptides or peptides spanning the central conserved region of the G protein could induce antibodies that blocked G protein CX3C-CX3CR1 interaction and disease pathogenesis mediated by RSV infection. The results show that mice vaccinated with G protein peptides or polypeptides containing the CX3C motif generate antibodies that inhibit G protein CX3C-CX3CR1 binding and chemotaxis, reduce lung virus titers, and prevent body weight loss and pulmonary inflammation. The results suggest that RSV vaccines that induce antibodies that block G protein CX3C-CX3CR1 interaction may offer a new, safe, and efficacious RSV vaccine strategy.

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Passive Transfer of Serum Antibodies Induced by BBG2Na, a Subunit Vaccine, in the Elderly Protects SCID Mouse Lungs Against Respiratory Syncytial Virus Challenge

Cited by 17 publications

References 25 publications

Small molecule inhibits respiratory syncytial virus entry and infection by blocking the interaction of the viral fusion protein with the cell membrane

Small molecule inhibits respiratory syncytial virus entry and infection by blocking the interaction of the viral fusion protein with the cell membrane

Therapeutic targeting of respiratory syncytial virus G-protein

Vaccination To Induce Antibodies Blocking the CX3C-CX3CR1 Interaction of Respiratory Syncytial Virus G Protein Reduces Pulmonary Inflammation and Virus Replication in Mice

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