A Single Dose of Modified Vaccinia Ankara expressing Ebola Virus Like Particles Protects Nonhuman Primates from Lethal Ebola Virus Challenge

被引：38

作者：

Domi, Arban ^{[1
]}

Feldmann, Friederike ^{[2
]}

Basu, Rahul ^{[1
]}

McCurley, Nathanael ^{[1
]}

Shifflett, Kyle ^{[3
]}

Emanuel, Jackson ^{[3
]}

Hellerstein, Michael S. ^{[1
]}

Guirakhoo, Farshad ^{[1
]}

Orlandi, Chiara ^{[4
]}

Flinko, Robin ^{[4
]}

Lewis, George K. ^{[4
]}

Hanley, Patrick W. ^{[2
]}

Feldmann, Heinz ^{[3
]}

Robinson, Harriet L. ^{[1
]}

Marzi, Andrea ^{[3
]}

机构：

[1] GeoVax Inc, Atlanta, GA 30080 USA

[2] NIAID, Rocky Mt Vet Branch, Div Intramural Res, NIH, Hamilton, MT USA

[3] NIAID, Lab Virol, Div Intramural Res, NIH, Hamilton, MT 59840 USA

[4] Univ Maryland, Sch Med, Inst Human Virol, Div Vaccine Res, Baltimore, MD 21201 USA

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

关键词：

DOUBLE-BLIND; IMMUNE-RESPONSES; RANDOMIZED-TRIAL; OPEN-LABEL; IMMUNOGENICITY; SAFETY; INFECTION; GLYCOPROTEIN; VACCINATION; MACAQUES;

D O I：

10.1038/s41598-017-19041-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Ebola virus (EBOV), isolate Makona, was the causative agent of the West African epidemic devastating predominantly Guinea, Liberia and Sierra Leone from 2013-2016. While several experimental vaccine and treatment approaches have been accelerated through human clinical trials, there is still no approved countermeasure available against this disease. Here, we report the construction and preclinical efficacy testing of a novel recombinant modified vaccinia Ankara (MVA)-based vaccine expressing the EBOV-Makona glycoprotein GP and matrix protein VP40 (MVA-EBOV). GP and VP40 form EBOV-like particles and elicit protective immune responses. In this study, we report 100% protection against lethal EBOV infection in guinea pigs after prime/boost vaccination with MVA-EBOV. Furthermore, this MVA-EBOV protected macaques from lethal disease after a single dose or prime/boost vaccination. The vaccine elicited a variety of antibody responses to both antigens, including neutralizing antibodies and antibodies with antibody-dependent cellular cytotoxic activity specific for GP. This is the first report that a replication-deficient MVA vector can confer full protection against lethal EBOV challenge after a single dose vaccination in macaques.

引用

页数：9

共 37 条

[1]

Agnandji S. T., 2015, NEW ENGLAND J MED

[2] Host range and cytopathogenicity of the highly attenuated MVA strain of vaccinia virus: Propagation and generation of recombinant viruses in a nonhuman mammalian cell line [J].

Carroll, MW ;

Moss, B .

VIROLOGY, 1997, 238 (02) :198-211

[3]

CDC, 2015, OUTBR CHRON EB VIR D

[4]

CDC, 2015, CHRON MARB HEM FEV O

[5]

Chippaux JP, 2014, J VENOM ANIM TOXINS, V20

[6] Safety and immunogenicity of a chimpanzee adenovirus-vectored Ebola vaccine in healthy adults: a randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a study [J].

De Santis, Olga ;

Audran, Regine ;

Pothin, Emilie ;

Warpelin-Decrausaz, Loane ;

Vallotton, Laure ;

Wuerzner, Gregoire ;

Cochet, Camille ;

Estoppey, Daniel ;

Steiner-Monard, Viviane ;

Lonchampt, Sophie ;

Thieny, Anne-Christine ;

Mayor, Carole ;

Bailer, Robert T. ;

Mbaya, Olivier Tshiani ;

Zhou, Yan ;

Ploquin, Aurelie ;

Sullivan, Nancy J. ;

Graham, Barney S. ;

Roman, Francois ;

De Ryck, Iris ;

Ballou, W. Ripley ;

Kieny, Marie Paule ;

Moorthy, Vasee ;

Spertini, Francois ;

Genton, Blaise .

LANCET INFECTIOUS DISEASES, 2016, 16 (03) :311-320

[7] Rapid protection in a monkeypox model by a single injection of a replication-deficient vaccinia virus [J].

Earl, Patricia L. ;

Americo, Jeffrey L. ;

Wyatt, Linda S. ;

Espenshade, Ondraya ;

Bassler, Jocelyn ;

Gong, Kathy ;

Lin, Shuling ;

Peters, Elizabeth ;

Rhodes, Lowrey, Jr. ;

Spano, Yvette Edghill ;

Silvera, Peter M. ;

Moss, Bernard .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (31) :10889-10894

[8] Prospective Surveillance for Cardiac Adverse Events in Healthy Adults Receiving Modified Vaccinia Ankara Vaccines: A Systematic Review [J].

Elizaga, Marnie L. ;

Vasan, Sandhya ;

Marovich, Mary A. ;

Sato, Alicia H. ;

Lawrence, Dale N. ;

Chaitman, Bernard R. ;

Frey, Sharon E. ;

Keefer, Michael C. .

PLOS ONE, 2013, 8 (01)

[9] Progress in filovirus vaccine development: evaluating the potential for clinical use [J].

Falzarano, Darryl ;

Geisbert, Thomas W. ;

Feldmann, Heinz .

EXPERT REVIEW OF VACCINES, 2011, 10 (01) :63-77

[10] Specificity and 6-Month Durability of Immune Responses Induced by DNA and Recombinant Modified Vaccinia Ankara Vaccines Expressing HIV-1 Virus-Like Particles [J].

Goepfert, Paul A. ;

Elizaga, Marnie L. ;

Seaton, Kelly ;

Tomaras, Georgia D. ;

Montefiori, David C. ;

Sato, Alicia ;

Hural, John ;

DeRosa, Stephen C. ;

Kalams, Spyros A. ;

McElrath, M. Juliana ;

Keefer, Michael C. ;

Baden, Lindsey R. ;

Lama, Javier R. ;

Sanchez, Jorge ;

Mulligan, Mark J. ;

Buchbinder, Susan P. ;

Hammer, Scott M. ;

Koblin, Beryl A. ;

Pensiero, Michael ;

Butler, Chris ;

Moss, Bernard ;

Robinson, Harriet L. .

JOURNAL OF INFECTIOUS DISEASES, 2014, 210 (01) :99-110

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