Safety, immunogenicity, and surrogate markers of clinical efficacy for modified vaccinia ankara as a smallpox vaccine in HIV-infected subjects

Richard N. Greenberg; Edgar Turner Overton; David W. Haas; Ian Frank; Mitchell Goldman; Alfred Von Krempelhuber; Garth Virgin; Nicole Bädeker; Jens Vollmar; Paul Chaplin

doi:10.1093/infdis/jis753

Safety, immunogenicity, and surrogate markers of clinical efficacy for modified vaccinia ankara as a smallpox vaccine in HIV-infected subjects

Richard N. Greenberg, Edgar Turner Overton, David W. Haas, Ian Frank, Mitchell Goldman, Alfred Von Krempelhuber, Garth Virgin, Nicole Bädeker, Jens Vollmar, Paul Chaplin

Internal Medicine

Research output: Contribution to journal › Article › peer-review

95 Scopus citations

Abstract

Background. Human immunodeficiency virus (HIV)-infected persons are at higher risk for serious complications associated with traditional smallpox vaccines. Alternative smallpox vaccines with an improved safety profile would address this unmet medical need.Methods. The safety and immunogenicity of modified vaccinia Ankara (MVA) was assessed in 91 HIV-infected adult subjects (CD4⁺ T-cell counts, ≥350 cells/mm³) and 60 uninfected volunteers. The primary objectives were to evaluate the safety of MVA and immunogenicity in HIV-infected and uninfected subjects. As a measure of the potential efficacy of MVA, the ability to boost the memory response in people previously vaccinated against smallpox was evaluated by the inclusion of vaccinia-experienced HIV-infected and HIV-uninfected subjects.Results. MVA was well tolerated and immunogenic in all subjects. Antibody responses were comparable between uninfected and HIV-infected populations, with only 1 significantly lower total antibody titer at 2 weeks after the second vaccination, while no significant differences were observed for neutralizing antibodies. MVA rapidly boosted the antibody responses in vaccinia-experienced subjects, supporting the efficacy of MVA against variola.Conclusions. MVA is a promising candidate as a safer smallpox vaccine, even for immunocompromised individuals, a group for whom current smallpox vaccines have an unacceptable safety profile.Clinical Trials Registration. NCT00189904.

Original language	English
Pages (from-to)	749-758
Number of pages	10
Journal	Journal of Infectious Diseases
Volume	207
Issue number	5
DOIs	https://doi.org/10.1093/infdis/jis753
State	Published - Mar 1 2013

Bibliographical note

Funding Information:
Potential conflicts of interest. All authors except for those employed by Bavarian Nordic received research grants from Bavarian Nordic to support the conduct of this trial. R. N. G. has also received research grants from Acambis, Boehringer-Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Wyeth, MBL, Dynport, VIRxSYS, Vaxpax, Emergent, Schering-Plough, and Tibotec. E. T. O. has also received research grants from Abbott, Gilead Sciences, GlaxoSmithKline, Merck, and Boehringer-Ingelheim and serves on advisory boards for Gilead, Bristol Meyers Squibb, GlaxoSmithKline, Tibotec, and Boehringer-Ingelheim. D. W. H. has also received research grants from Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Merck, Tanox, and Tibotec and is on scientific advisory boards for GlaxoSmithKline and Tibotec. I. F. has received research grants from GlaxoSmithKline and is an advisor for Gilead. M. G. has received research grants from Pfizer, GlaxoSmithKline, and Schering-Plough. A. v. K., J. V., G. V., N. B., and P. C. were employees of Bavarian Nordic.

Funding Information:
Financial support. This work was supported by the DMID (contract N01-AI-40072), the GCRC Grant NIH MO1 RR000750-36 to the Indiana University School of Medicine and the Penn Center for AIDS Research Grant P30AI045008 to the University of Pennsylvania.

Keywords

HIV
MVA
Smallpox
vaccine

ASJC Scopus subject areas

General Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/infdis/jis753

Cite this

Greenberg, R. N., Overton, E. T., Haas, D. W., Frank, I., Goldman, M., Von Krempelhuber, A., Virgin, G., Bädeker, N., Vollmar, J., & Chaplin, P. (2013). Safety, immunogenicity, and surrogate markers of clinical efficacy for modified vaccinia ankara as a smallpox vaccine in HIV-infected subjects. Journal of Infectious Diseases, 207(5), 749-758. https://doi.org/10.1093/infdis/jis753

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abstract = "Background. Human immunodeficiency virus (HIV)-infected persons are at higher risk for serious complications associated with traditional smallpox vaccines. Alternative smallpox vaccines with an improved safety profile would address this unmet medical need.Methods. The safety and immunogenicity of modified vaccinia Ankara (MVA) was assessed in 91 HIV-infected adult subjects (CD4+ T-cell counts, ≥350 cells/mm3) and 60 uninfected volunteers. The primary objectives were to evaluate the safety of MVA and immunogenicity in HIV-infected and uninfected subjects. As a measure of the potential efficacy of MVA, the ability to boost the memory response in people previously vaccinated against smallpox was evaluated by the inclusion of vaccinia-experienced HIV-infected and HIV-uninfected subjects.Results. MVA was well tolerated and immunogenic in all subjects. Antibody responses were comparable between uninfected and HIV-infected populations, with only 1 significantly lower total antibody titer at 2 weeks after the second vaccination, while no significant differences were observed for neutralizing antibodies. MVA rapidly boosted the antibody responses in vaccinia-experienced subjects, supporting the efficacy of MVA against variola.Conclusions. MVA is a promising candidate as a safer smallpox vaccine, even for immunocompromised individuals, a group for whom current smallpox vaccines have an unacceptable safety profile.Clinical Trials Registration. NCT00189904.",

keywords = "HIV, MVA, Smallpox, vaccine",

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note = "Funding Information: Potential conflicts of interest. All authors except for those employed by Bavarian Nordic received research grants from Bavarian Nordic to support the conduct of this trial. R. N. G. has also received research grants from Acambis, Boehringer-Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Wyeth, MBL, Dynport, VIRxSYS, Vaxpax, Emergent, Schering-Plough, and Tibotec. E. T. O. has also received research grants from Abbott, Gilead Sciences, GlaxoSmithKline, Merck, and Boehringer-Ingelheim and serves on advisory boards for Gilead, Bristol Meyers Squibb, GlaxoSmithKline, Tibotec, and Boehringer-Ingelheim. D. W. H. has also received research grants from Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Merck, Tanox, and Tibotec and is on scientific advisory boards for GlaxoSmithKline and Tibotec. I. F. has received research grants from GlaxoSmithKline and is an advisor for Gilead. M. G. has received research grants from Pfizer, GlaxoSmithKline, and Schering-Plough. A. v. K., J. V., G. V., N. B., and P. C. were employees of Bavarian Nordic. Funding Information: Financial support. This work was supported by the DMID (contract N01-AI-40072), the GCRC Grant NIH MO1 RR000750-36 to the Indiana University School of Medicine and the Penn Center for AIDS Research Grant P30AI045008 to the University of Pennsylvania.",

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Greenberg, RN, Overton, ET, Haas, DW, Frank, I, Goldman, M, Von Krempelhuber, A, Virgin, G, Bädeker, N, Vollmar, J & Chaplin, P 2013, 'Safety, immunogenicity, and surrogate markers of clinical efficacy for modified vaccinia ankara as a smallpox vaccine in HIV-infected subjects', Journal of Infectious Diseases, vol. 207, no. 5, pp. 749-758. https://doi.org/10.1093/infdis/jis753

TY - JOUR

T1 - Safety, immunogenicity, and surrogate markers of clinical efficacy for modified vaccinia ankara as a smallpox vaccine in HIV-infected subjects

AU - Greenberg, Richard N.

AU - Overton, Edgar Turner

AU - Haas, David W.

AU - Frank, Ian

AU - Goldman, Mitchell

AU - Von Krempelhuber, Alfred

AU - Virgin, Garth

AU - Bädeker, Nicole

AU - Vollmar, Jens

AU - Chaplin, Paul

N1 - Funding Information: Potential conflicts of interest. All authors except for those employed by Bavarian Nordic received research grants from Bavarian Nordic to support the conduct of this trial. R. N. G. has also received research grants from Acambis, Boehringer-Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Wyeth, MBL, Dynport, VIRxSYS, Vaxpax, Emergent, Schering-Plough, and Tibotec. E. T. O. has also received research grants from Abbott, Gilead Sciences, GlaxoSmithKline, Merck, and Boehringer-Ingelheim and serves on advisory boards for Gilead, Bristol Meyers Squibb, GlaxoSmithKline, Tibotec, and Boehringer-Ingelheim. D. W. H. has also received research grants from Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Merck, Tanox, and Tibotec and is on scientific advisory boards for GlaxoSmithKline and Tibotec. I. F. has received research grants from GlaxoSmithKline and is an advisor for Gilead. M. G. has received research grants from Pfizer, GlaxoSmithKline, and Schering-Plough. A. v. K., J. V., G. V., N. B., and P. C. were employees of Bavarian Nordic. Funding Information: Financial support. This work was supported by the DMID (contract N01-AI-40072), the GCRC Grant NIH MO1 RR000750-36 to the Indiana University School of Medicine and the Penn Center for AIDS Research Grant P30AI045008 to the University of Pennsylvania.

PY - 2013/3/1

Y1 - 2013/3/1

N2 - Background. Human immunodeficiency virus (HIV)-infected persons are at higher risk for serious complications associated with traditional smallpox vaccines. Alternative smallpox vaccines with an improved safety profile would address this unmet medical need.Methods. The safety and immunogenicity of modified vaccinia Ankara (MVA) was assessed in 91 HIV-infected adult subjects (CD4+ T-cell counts, ≥350 cells/mm3) and 60 uninfected volunteers. The primary objectives were to evaluate the safety of MVA and immunogenicity in HIV-infected and uninfected subjects. As a measure of the potential efficacy of MVA, the ability to boost the memory response in people previously vaccinated against smallpox was evaluated by the inclusion of vaccinia-experienced HIV-infected and HIV-uninfected subjects.Results. MVA was well tolerated and immunogenic in all subjects. Antibody responses were comparable between uninfected and HIV-infected populations, with only 1 significantly lower total antibody titer at 2 weeks after the second vaccination, while no significant differences were observed for neutralizing antibodies. MVA rapidly boosted the antibody responses in vaccinia-experienced subjects, supporting the efficacy of MVA against variola.Conclusions. MVA is a promising candidate as a safer smallpox vaccine, even for immunocompromised individuals, a group for whom current smallpox vaccines have an unacceptable safety profile.Clinical Trials Registration. NCT00189904.

AB - Background. Human immunodeficiency virus (HIV)-infected persons are at higher risk for serious complications associated with traditional smallpox vaccines. Alternative smallpox vaccines with an improved safety profile would address this unmet medical need.Methods. The safety and immunogenicity of modified vaccinia Ankara (MVA) was assessed in 91 HIV-infected adult subjects (CD4+ T-cell counts, ≥350 cells/mm3) and 60 uninfected volunteers. The primary objectives were to evaluate the safety of MVA and immunogenicity in HIV-infected and uninfected subjects. As a measure of the potential efficacy of MVA, the ability to boost the memory response in people previously vaccinated against smallpox was evaluated by the inclusion of vaccinia-experienced HIV-infected and HIV-uninfected subjects.Results. MVA was well tolerated and immunogenic in all subjects. Antibody responses were comparable between uninfected and HIV-infected populations, with only 1 significantly lower total antibody titer at 2 weeks after the second vaccination, while no significant differences were observed for neutralizing antibodies. MVA rapidly boosted the antibody responses in vaccinia-experienced subjects, supporting the efficacy of MVA against variola.Conclusions. MVA is a promising candidate as a safer smallpox vaccine, even for immunocompromised individuals, a group for whom current smallpox vaccines have an unacceptable safety profile.Clinical Trials Registration. NCT00189904.

KW - HIV

KW - MVA

KW - Smallpox

KW - vaccine

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Safety, immunogenicity, and surrogate markers of clinical efficacy for modified vaccinia ankara as a smallpox vaccine in HIV-infected subjects

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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