Tags

Type your tag names separated by a space and hit enter

A humanized monoclonal antibody neutralizes yellow fever virus strain 17D-204 in vitro but does not protect a mouse model from disease.
Antiviral Res. 2016 07; 131:92-9.AR

Abstract

The yellow fever virus (YFV) vaccine 17D-204 is considered safe and effective, yet rare severe adverse events (SAEs), some resulting in death, have been documented following vaccination. Individuals exhibiting post-vaccinal SAEs are ideal candidates for antiviral monoclonal antibody (MAb) therapy; the time until appearance of clinical signs post-exposure is usually short and patients are quickly hospitalized. We previously developed a murine-human chimeric monoclonal antibody (cMAb), 2C9-cIgG, reactive with both virulent YFV and 17D-204, and demonstrated its ability to prevent and treat YF disease in both AG129 mouse and hamster models of infection. To counteract possible selection of 17D-204 variants that escape neutralization by treatment with a single MAb (2C9-cIgG), we developed a second cMAb, 864-cIgG, for use in combination with 2C9-cIgG in post-vaccinal therapy. MAb 864-cIgG recognizes/neutralizes only YFV 17D-204 vaccine substrain and binds to domain III (DIII) of the viral envelope protein, which is different from the YFV type-specific binding site of 2C9-cIgG in DII. Although it neutralized 17D-204 in vitro, administration of 864-cIgG had no protective capacity in the interferon receptor-deficient AG129 mouse model of 17D-204 infection. The data presented here show that although DIII-specific 864-cIgG neutralizes virus infectivity in vitro, it does not have the ability to abrogate disease in vivo. Therefore, combination of 864-cIgG with 2C9-cIgG for treatment of YF vaccination SAEs does not appear to provide an improvement on 2C9-cIgG therapy alone.

Authors+Show Affiliations

Division of Vector-Borne Diseases, U.S. Centers for Disease Control and Prevention, Fort Collins, CO, 80521, USA.Division of Vector-Borne Diseases, U.S. Centers for Disease Control and Prevention, Fort Collins, CO, 80521, USA.Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, 80523-1692, USA.Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, 80523-1692, USA.Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, 80523-1692, USA.Department of Pathology and Sealy Center for Vaccine Development, University of Texas-Medical Branch, Galveston, TX, 77555, USA.Division of Vector-Borne Diseases, U.S. Centers for Disease Control and Prevention, Fort Collins, CO, 80521, USA.Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, 80523-1692, USA. Electronic address: carol.blair@colostate.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

27126613

Citation

Calvert, Amanda E., et al. "A Humanized Monoclonal Antibody Neutralizes Yellow Fever Virus Strain 17D-204 in Vitro but Does Not Protect a Mouse Model From Disease." Antiviral Research, vol. 131, 2016, pp. 92-9.
Calvert AE, Dixon KL, Piper J, et al. A humanized monoclonal antibody neutralizes yellow fever virus strain 17D-204 in vitro but does not protect a mouse model from disease. Antiviral Res. 2016;131:92-9.
Calvert, A. E., Dixon, K. L., Piper, J., Bennett, S. L., Thibodeaux, B. A., Barrett, A. D., Roehrig, J. T., & Blair, C. D. (2016). A humanized monoclonal antibody neutralizes yellow fever virus strain 17D-204 in vitro but does not protect a mouse model from disease. Antiviral Research, 131, 92-9. https://doi.org/10.1016/j.antiviral.2016.04.013
Calvert AE, et al. A Humanized Monoclonal Antibody Neutralizes Yellow Fever Virus Strain 17D-204 in Vitro but Does Not Protect a Mouse Model From Disease. Antiviral Res. 2016;131:92-9. PubMed PMID: 27126613.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A humanized monoclonal antibody neutralizes yellow fever virus strain 17D-204 in vitro but does not protect a mouse model from disease. AU - Calvert,Amanda E, AU - Dixon,Kandice L, AU - Piper,Joseph, AU - Bennett,Susan L, AU - Thibodeaux,Brett A, AU - Barrett,Alan D T, AU - Roehrig,John T, AU - Blair,Carol D, Y1 - 2016/04/26/ PY - 2015/12/14/received PY - 2016/04/20/revised PY - 2016/04/23/accepted PY - 2016/4/30/entrez PY - 2016/4/30/pubmed PY - 2017/11/7/medline KW - Monoclonal antibody therapy KW - Neutralizing antibody KW - Post-vaccinal SAE KW - YFV vaccine SP - 92 EP - 9 JF - Antiviral research JO - Antiviral Res VL - 131 N2 - The yellow fever virus (YFV) vaccine 17D-204 is considered safe and effective, yet rare severe adverse events (SAEs), some resulting in death, have been documented following vaccination. Individuals exhibiting post-vaccinal SAEs are ideal candidates for antiviral monoclonal antibody (MAb) therapy; the time until appearance of clinical signs post-exposure is usually short and patients are quickly hospitalized. We previously developed a murine-human chimeric monoclonal antibody (cMAb), 2C9-cIgG, reactive with both virulent YFV and 17D-204, and demonstrated its ability to prevent and treat YF disease in both AG129 mouse and hamster models of infection. To counteract possible selection of 17D-204 variants that escape neutralization by treatment with a single MAb (2C9-cIgG), we developed a second cMAb, 864-cIgG, for use in combination with 2C9-cIgG in post-vaccinal therapy. MAb 864-cIgG recognizes/neutralizes only YFV 17D-204 vaccine substrain and binds to domain III (DIII) of the viral envelope protein, which is different from the YFV type-specific binding site of 2C9-cIgG in DII. Although it neutralized 17D-204 in vitro, administration of 864-cIgG had no protective capacity in the interferon receptor-deficient AG129 mouse model of 17D-204 infection. The data presented here show that although DIII-specific 864-cIgG neutralizes virus infectivity in vitro, it does not have the ability to abrogate disease in vivo. Therefore, combination of 864-cIgG with 2C9-cIgG for treatment of YF vaccination SAEs does not appear to provide an improvement on 2C9-cIgG therapy alone. SN - 1872-9096 UR - https://www.unboundmedicine.com/medline/citation/27126613/A_humanized_monoclonal_antibody_neutralizes_yellow_fever_virus_strain_17D_204_in_vitro_but_does_not_protect_a_mouse_model_from_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-3542(16)30242-X DB - PRIME DP - Unbound Medicine ER -