scholarly journals A Cross-Reactive Humanized Monoclonal Antibody Targeting Fusion Glycoprotein Function Protects Ferrets Against Lethal Nipah Virus and Hendra Virus Infection

2019 ◽  
Vol 221 (Supplement_4) ◽  
pp. S471-S479 ◽  
Author(s):  
Chad E Mire ◽  
Yee-Peng Chan ◽  
Viktoriya Borisevich ◽  
Robert W Cross ◽  
Lianying Yan ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Virus Infection ◽  
Severe Disease ◽  
Human Monoclonal Antibody ◽  
Nipah Virus ◽  
Antibody Therapy ◽  
Hendra Virus ◽  
High Dose ◽  
Virus Challenge

Abstract Background Nipah virus (NiV) and Hendra virus (HeV) are zoonotic paramyxoviruses that cause severe disease in both animals and humans. There are no approved vaccines or treatments for use in humans; however, therapeutic treatment of both NiV and HeV infection in ferrets and non-human primates with a cross-reactive, neutralizing human monoclonal antibody (mAb), m102.4, targeting the G glycoprotein has been demonstrated. In a previous study, we isolated, characterized, and humanized a cross-reactive, neutralizing anti-F mAb (h5B3.1). The mAb h5B3.1 blocks the required F conformational change needed to facilitate membrane fusion and virus infection, and the epitope recognized by h5B3.1 has been structurally defined; however, the efficacy of h5B3.1 in vivo is unknown. Methods The post-infection antiviral activity of h5B3.1 was evaluated in vivo by administration in ferrets after NiV and HeV virus challenge. Results All subjects that received h5B3.1 from 1 to several days after infection with a high-dose, oral-nasal virus challenge were protected from disease, whereas all controls died. Conclusions This is the first successful post-exposure antibody therapy for NiV and HeV using a humanized cross-reactive mAb targeting the F glycoprotein, and the findings suggest that a combination therapy targeting both F and G should be evaluated as a therapy for NiV/HeV infection.

scholarly journals Chloroquine Administration Does Not Prevent Nipah Virus Infection and Disease in Ferrets

2009 ◽  
Vol 83 (22) ◽  
pp. 11979-11982 ◽  
Author(s):  
Jackie Pallister ◽  
Deborah Middleton ◽  
Gary Crameri ◽  
Manabu Yamada ◽  
Reuben Klein ◽  
...  
Keyword(s):  
Virus Infection ◽  
Nipah Virus ◽  
Disease Outbreaks ◽  
Mortality Rates ◽  
Hendra Virus ◽  
Malaria Therapy ◽  
Sporadic Disease

ABSTRACT Hendra virus and Nipah virus, two zoonotic paramyxoviruses in the genus Henipavirus, have recently emerged and continue to cause sporadic disease outbreaks in humans and animals. Mortality rates of up to 75% have been reported in humans, but there are presently no clinically licensed therapeutics for treating henipavirus-induced disease. A recent report indicated that chloroquine, used in malaria therapy for over 70 years, prevented infection with Nipah virus in vitro. Chloroquine was assessed using a ferret model of lethal Nipah virus infection and found to be ineffective against Nipah virus infection in vivo.

scholarly journals Heterosubtypic Protection Conferred by the Human Monoclonal Antibody PN-SIA28 against Influenza A Virus Lethal Infections in Mice

2015 ◽  
Vol 59 (5) ◽  
pp. 2647-2653 ◽  
Author(s):  
Miguel Retamal ◽  
Yacine Abed ◽  
Chantal Rhéaume ◽  
Francesca Cappelletti ◽  
Nicola Clementi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Body Weight ◽  
Influenza Virus ◽  
Influenza A ◽  
Human Monoclonal Antibody ◽  
Influenza A Viruses ◽  
Virus Challenge ◽  
Influenza A H1n1

ABSTRACTPN-SIA28 is a human monoclonal antibody (Hu-MAb) targeting highly conserved epitopes within the stem portion of the influenza virus hemagglutinin (HA) (N. Clementi, et al, PLoS One 6:e28001, 2011,http://dx.doi.org/10.1371/journal.pone.0028001). Previousin vitrostudies demonstrated PN-SIA28 neutralizing activities against phylogenetically divergent influenza A subtypes. In this study, the protective activity of PN-SIA28 was evaluated in mice inoculated with lethal influenza A/WSN/33 (H1N1), A/Quebec/144147/09 (H1N1)pdm09, and A/Victoria/3/75 (H3N2) viruses. At 24 h postinoculation (p.i.), animals received PN-SIA28 intraperitoneally (1 or 10 mg/kg of body weight) or 10 mg/kg of unrelated Hu-MAb (mock). Body weight loss and mortality rate (MR) were recorded for 14 days postinfection (p.i.). Lung viral titers (LVT) were determined at day 5 p.i. In A/WSN/33 (H1N1)-infected groups, all untreated and mock-receiving mice died, whereas MRs of 87.5% and 25% were observed in mice that received PN-SIA28 1 and 10 mg/kg, respectively. In influenza A(H1N1) pdm09-infected groups, an MR of 75% was recorded for untreated and mock-treated groups, whereas the PN-SIA28 1-mg/kg and 10-mg/kg groups had rates of 62.5% and 0%, respectively. In A/Victoria/3/75 (H3N2)-infected animals, untreated and mock-treated animals had MRs of 37.5% and 25%, respectively, and no mortalities were recorded after PN-SIA28 treatments. Accordingly, PN-SIA28 treatments significantly reduced weight losses and resulted in a ≥1-log reduction in LVT compared to the control in all infection groups. This study confirms that antibodies targeting highly conserved epitopes in the influenza HA stem region, like PN-SIA28, not only neutralize influenza A viruses of clinically relevant subtypesin vitrobut also, more importantly, protect from a lethal influenza virus challengein vivo.

scholarly journals Therapeutic Treatment of Nipah Virus Infection in Nonhuman Primates with a Neutralizing Human Monoclonal Antibody

2014 ◽  
Vol 6 (242) ◽  
pp. 242ra82-242ra82 ◽  
Author(s):  
T. W. Geisbert ◽  
C. E. Mire ◽  
J. B. Geisbert ◽  
Y.-P. Chan ◽  
K. N. Agans ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Virus Infection ◽  
Nonhuman Primates ◽  
Human Monoclonal Antibody ◽  
Nipah Virus ◽  
Therapeutic Treatment

Reshaping a Human Monoclonal Antibody to Inhibit Human Respiratory Syncytial Virus Infection in Vivo

1991 ◽  
Vol 9 (3) ◽  
pp. 266-271 ◽  
Author(s):  
Philip R. Tempest ◽  
Patricia Bremner ◽  
Martin Lambert ◽  
Geraldine Taylor ◽  
Julie M. Furze ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Respiratory Syncytial Virus ◽  
Virus Infection ◽  
Respiratory Syncytial Virus Infection ◽  
Human Monoclonal Antibody ◽  
Human Respiratory Syncytial Virus ◽  
Syncytial Virus

scholarly journals Repeated Low-Dose Influenza Virus Infection Causes Severe Disease in Mice: a Model for Vaccine Evaluation

2015 ◽  
Vol 89 (15) ◽  
pp. 7841-7851 ◽  
Author(s):  
Yufeng Song ◽  
Xiang Wang ◽  
Hongbo Zhang ◽  
Xinying Tang ◽  
Min Li ◽  
...  
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Low Dose ◽  
Severe Disease ◽  
Influenza Vaccines ◽  
High Dose ◽  
Single High Dose ◽  
Virus Challenge ◽  
Cell Responses

ABSTRACTInfluenza infection causes severe disease and death in humans. In traditional vaccine research and development, a single high-dose virus challenge of animals is used to evaluate vaccine efficacy. This type of challenge model may have limitations. In the present study, we developed a novel challenge model by infecting mice repeatedly in short intervals with low doses of influenza A virus. Our results show that compared to a single high-dose infection, mice that received repeated low-dose challenges showed earlier morbidity and mortality and more severe disease. They developed higher vial loads, more severe lung pathology, and greater inflammatory responses and generated only limited influenza A virus-specific B and T cell responses. A commercial trivalent influenza vaccine protected mice against a single high and lethal dose of influenza A virus but was ineffective against repeated low-dose virus challenges. Overall, our data show that the repeated low-dose influenza A virus infection mouse model is more stringent and may thus be more suitable to select for highly efficacious influenza vaccines.IMPORTANCEInfluenza epidemics and pandemics pose serious threats to public health. Animal models are crucial for evaluating the efficacy of influenza vaccines. Traditional models based on a single high-dose virus challenge may have limitations. Here, we describe a new mouse model based on repeated low-dose influenza A virus challenges given within a short period. Repeated low-dose challenges caused more severe disease in mice, associated with higher viral loads and increased lung inflammation and reduced influenza A virus-specific B and T cell responses. A commercial influenza vaccine that was shown to protect mice from high-dose challenge was ineffective against repeated low-dose challenges. Overall, our results show that the low-dose repeated-challenge model is more stringent and may therefore be better suited for preclinical vaccine efficacy studies.

scholarly journals A Neutralizing Human Monoclonal Antibody Protects African Green Monkeys from Hendra Virus Challenge

2011 ◽  
Vol 3 (105) ◽  
pp. 105ra103-105ra103 ◽  
Author(s):  
K. N. Bossart ◽  
T. W. Geisbert ◽  
H. Feldmann ◽  
Z. Zhu ◽  
F. Feldmann ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Human Monoclonal Antibody ◽  
Hendra Virus ◽  
Virus Challenge ◽  
Green Monkeys

scholarly journals A Neutralizing Human Monoclonal Antibody Protects against Lethal Disease in a New Ferret Model of Acute Nipah Virus Infection

2009 ◽  
Vol 5 (10) ◽  
pp. e1000642 ◽  
Author(s):  
Katharine N. Bossart ◽  
Zhongyu Zhu ◽  
Deborah Middleton ◽  
Jessica Klippel ◽  
Gary Crameri ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Virus Infection ◽  
Human Monoclonal Antibody ◽  
Nipah Virus

scholarly journals A novel neutralizing human monoclonal antibody broadly abrogates hepatitis C virus infection in vitro and in vivo

2017 ◽  
Vol 148 ◽  
pp. 53-64 ◽  
Author(s):  
Isabelle Desombere ◽  
Ahmed Atef Mesalam ◽  
Richard A. Urbanowicz ◽  
Freya Van Houtte ◽  
Lieven Verhoye ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Human Monoclonal Antibody ◽  
Hepatitis C Virus Infection

scholarly journals Evaluation of Fab and F(ab′)2 Fragments and Isotype Variants of a Recombinant Human Monoclonal Antibody against Shiga Toxin 2

2010 ◽  
Vol 78 (3) ◽  
pp. 1376-1382 ◽  
Author(s):  
Donna E. Akiyoshi ◽  
Abhineet S. Sheoran ◽  
Curtis M. Rich ◽  
L. Richard ◽  
Susan Chapman-Bonofiglio ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Shiga Toxin ◽  
Chinese Hamster Ovary Cells ◽  
Human Monoclonal Antibody ◽  
Chinese Hamster ◽  
The Body ◽  
Neutralization Activity ◽  
Shiga Toxin 2

ABSTRACT 5C12 HuMAb is a human monoclonal antibody against the A subunit of Shiga toxin 2 (Stx2). We have previously shown that 5C12 HuMAb effectively neutralizes the cytotoxic effects of this toxin by redirecting its transport within the cell and also by neutralizing the toxin's ability to inhibit protein synthesis. The 5C12 HuMAb and its recombinant IgG1 version protect mice at a dose of 0.6 μg against a lethal challenge of Stx2. The contribution of the Fc region to this observed neutralization activity of the 5C12 antibody against Stx2 was investigated in this study. Using recombinant DNA technology, 5C12 isotype variants (IgG1, IgG2, IgG3, and IgG4) and antibody fragments [Fab, F(ab′)2] were expressed in Chinese hamster ovary cells and evaluated in vitro and in vivo. All four 5C12 isotype variants showed protection in vitro, with the IgG3 and IgG4 variants showing the highest protection in vivo. The Fab and F(ab′)2 fragments also showed protection in vitro but no protection in the mouse toxicity model. Similar results were obtained for a second HuMAb (5H8) against the B subunit of Stx2. The data suggest the importance of the Fc region for neutralization activity, but it is not clear if this is related to the stability of the full-length antibody or if the Fc region is required for effective elimination of the toxin from the body.

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