Randomized, Blinded, Dose-Ranging Trial of an Ebola Virus Glycoprotein Nanoparticle Vaccine With Matrix-M Adjuvant in Healthy Adults

被引：31

作者：

Fries, Louis ^{[1
]}

Cho, Iksung ^{[1
]}

Kraehling, Verena ^{[2
,3
]}

Fehling, Sarah K. ^{[2
]}

Strecker, Thomas ^{[2
]}

Becker, Stephan ^{[2
,3
]}

Hooper, Jay W. ^{[4
]}

Kwilas, Steven A. ^{[4
]}

Agrawal, Sapeckshita ^{[1
]}

Wen, Judy ^{[1
]}

Lewis, Maggie ^{[1
]}

Fix, Amy ^{[1
]}

Thomas, Nigel ^{[1
]}

Flyer, David ^{[1
]}

Smith, Gale ^{[1
]}

Glenn, Gregory ^{[1
]}

机构：

[1] Novavax Inc, 21 Firstlield Rd, Gaithersburg, MD 20878 USA

[2] Philipps Univ Marburg, Inst Virol, Marburg, Germany

[3] German Ctr Infect Res DZIF, Partner Site Giessen Marburg Langen, Marburg, Germany

[4] US Army, Med Res Inst Infect Dis, Ft Detrick, MD USA

来源：

JOURNAL OF INFECTIOUS DISEASES | 2020年 / 222卷 / 04期

关键词：

Ebola virus; glycoprotein; Matrix-M adjuvant; nanoparticle vaccine; ANTIBODY; SAFETY; IMMUNOGENICITY; DISEASE;

D O I：

10.1093/infdis/jiz518

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background. Ebola virus (EBOV) epidemics pose a major public health risk. There currently is no licensed human vaccine against EBOV. The safety and immunogenicity of a recombinant EBOV glycoprotein (GP) nanoparticle vaccine formulated with or without Matrix-M adjuvant were evaluated to support vaccine development. Methods. A phase 1, placebo-controlled, dose-escalation trial was conducted in 230 healthy adults to evaluate 4 EBOV GP antigen doses as single- or 2-dose regimens with or without adjuvant. Safety and immunogenicity were assessed through 1-year postdosing. Results. All EBOV GP vaccine formulations were well tolerated. Receipt of 2 doses of EBOV GP with adjuvant showed a rapid increase in anti-EBOV GP immunoglobulin G titers with peak titers observed on Day 35 representing 498- to 754-fold increases from baseline; no evidence of an antigen dose response was observed. Serum EBOV-neutralizing and binding antibodies using wild-type Zaire EBOV (ZEBOV) or pseudovirion assays were 3- to 9-fold higher among recipients of 2-dose EBOV GP with adjuvant, compared with placebo on Day 35, which persisted through 1 year. Conclusions. Ebola virus GP vaccine with Matrix-M adjuvant is well tolerated and elicits a robust and persistent immune response. These data suggest that further development of this candidate vaccine for prevention of EBOV disease is warranted.

引用

页码：572 / 582

页数：11

共 25 条

[1] Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe [J].

Agnandji, S. T. ;

Huttner, A. ;

Zinser, M. E. ;

Njuguna, P. ;

Dahlke, C. ;

Fernandes, J. F. ;

Yerly, S. ;

Dayer, J. -A. ;

Kraehling, V. ;

Kasonta, R. ;

Adegnika, A. A. ;

Altfeld, M. ;

Auderset, F. ;

Bache, E. B. ;

Biedenkopf, N. ;

Borregaard, S. ;

Brosnahan, J. S. ;

Burrow, R. ;

Combescure, C. ;

Desmeules, J. ;

Eickmann, M. ;

Fehling, S. K. ;

Finckh, A. ;

Goncalves, A. R. ;

Grobusch, M. P. ;

Hooper, J. ;

Jambrecina, A. ;

Kabwende, A. L. ;

Kaya, G. ;

Kimani, D. ;

Lell, B. ;

Lemaitre, B. ;

Lohse, A. W. ;

Massinga-Loembe, M. ;

Matthey, A. ;

Mordmueller, B. ;

Nolting, A. ;

Ogwang, C. ;

Ramharter, M. ;

Schmidt-Chanasit, J. ;

Schmiedel, S. ;

Silvera, P. ;

Stahl, F. R. ;

Staines, H. M. ;

Strecker, T. ;

Stubbe, H. C. ;

Tsofa, B. ;

Zaki, S. ;

Fast, P. ;

Moorthy, V. .

NEW ENGLAND JOURNAL OF MEDICINE, 2016, 374 (17) :1647-1660

[2] Safety and immunogenicity of rVSVΔG-ZEBOV-GP Ebola vaccine in adults and children in Lambarene A, Gabon: A phase I randomised trial [J].

Agnandji, Selidji T. ;

Fernandes, Jose F. ;

Bache, Emmanuel B. ;

Obiang, Regis M. ;

Brosnahan, Jessica S. ;

Kabwende, Lumeka ;

Pitzinger, Paul ;

Staarink, Pieter ;

Massinga-Loembe, Marguerite ;

Kraehling, Verena ;

Biedenkopf, Nadine ;

Fehling, Sarah Katharina ;

Strecker, Thomas ;

Clark, David J. ;

Staines, Henry M. ;

Hooper, Jay W. ;

Silvera, Peter ;

Moorthy, Vasee ;

Kieny, Marie-Paule ;

Adegnika, Akim A. ;

Grobusch, Martin P. ;

Becker, Stephan ;

Ramharter, Michael ;

Mordmueller, Benjamin ;

Lell, Bertrand ;

Krishna, Sanjeev ;

Kremsner, Peter G. .

PLOS MEDICINE, 2017, 14 (10)

[3] Matrix-M adjuvant enhances antibody, cellular and protective immune responses of a Zaire Ebola/Makona virus glycoprotein (GP) nanoparticle vaccine in mice [J].

Bengtsson, Karin Lovgren ;

Song, Haifeng ;

Stertman, Linda ;

Liu, Ye ;

Flyer, David C. ;

Massare, Michael J. ;

Xu, Ren-Huan ;

Zhou, Bin ;

Lu, Hanxin ;

Kwilas, Steve A. ;

Hahn, Timothy J. ;

Kpamegan, Eloi ;

Hooper, Jay ;

Carrion, Ricardo, Jr. ;

Glenn, Gregory ;

Smith, Gale .

VACCINE, 2016, 34 (16) :1927-1935

[4] Production of Potent Fully Human Polyclonal Antibodies against Ebola Zaire Virus in Transchromosomal Cattle [J].

Dye, John M. ;

Wu, Hua ;

Hooper, Jay W. ;

Khurana, Surender ;

Kuehne, Ana I. ;

Coyle, Elizabeth M. ;

Ortiz, Ramon A. ;

Fuentes, Sandra ;

Herbert, Andrew S. ;

Golding, Hana ;

Bakken, Russell A. ;

Brannan, Jennifer M. ;

Kwilas, Steve A. ;

Sullivan, Eddie J. ;

Luke, Thomas C. ;

Smith, Gale ;

Glenn, Gregory ;

Li, Wenfang ;

Ye, Ling ;

Yang, Chinglai ;

Compans, Richard W. ;

Tripp, Ralph A. ;

Jiao, Jin-an .

SCIENTIFIC REPORTS, 2016, 6

[5] A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA [J].

Ewer, K. ;

Rampling, T. ;

Venkatraman, N. ;

Bowyer, G. ;

Wright, D. ;

Lambe, T. ;

Imoukhuede, E. B. ;

Payne, R. ;

Fehling, S. K. ;

Strecker, T. ;

Biedenkopf, N. ;

Kraehling, V. ;

Tully, C. M. ;

Edwards, N. J. ;

Bentley, E. M. ;

Samuel, D. ;

Labbe, G. ;

Jin, J. ;

Gibani, M. ;

Minhinnick, A. ;

Wilkie, M. ;

Poulton, I. ;

Lella, N. ;

Roberts, R. ;

Hartnell, F. ;

Bliss, C. ;

Sierra-Davidson, K. ;

Powlson, J. ;

Berrie, E. ;

Tedder, R. ;

Roman, F. ;

De Ryck, I. ;

Nicosia, A. ;

Sullivan, N. J. ;

Stanley, D. A. ;

Mbaya, O. T. ;

Ledgerwood, J. E. ;

Schwartz, R. M. ;

Siani, L. ;

Colloca, S. ;

Folgori, A. ;

Di Marco, S. ;

Cortese, R. ;

Wright, E. ;

Becker, S. ;

Graham, B. S. ;

Koup, R. A. ;

Levine, M. M. ;

Volkmann, A. ;

Chaplin, P. .

NEW ENGLAND JOURNAL OF MEDICINE, 2016, 374 (17) :1635-1646

[6] A Recombinant Viruslike Particle Influenza A (H7N9) Vaccine [J].

Fries, Louis F. ;

Smith, Gale E. ;

Glenn, Gregory M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (26) :2564-2566

[7] A Randomized, Blinded, Controlled, Dose-Ranging Study of a Respiratory Syncytial Virus Recombinant Fusion (F) Nanoparticle Vaccine in Healthy Women of Childbearing Age [J].

Glenn, Gregory M. ;

Fries, Louis F. ;

Thomas, D. Nigel ;

Smith, Gale ;

Kpamegan, Eloi ;

Lu, Hanxin ;

Flyer, David ;

Jani, Dewal ;

Hickman, Somia P. ;

Piedra, Pedro A. .

JOURNAL OF INFECTIOUS DISEASES, 2016, 213 (03) :411-422

[8] Safety and immunogenicity of a Sf9 insect cell-derived respiratory syncytial virus fusion protein nanoparticle vaccine [J].

Glenn, Gregory M. ;

Smith, Gale ;

Fries, Louis ;

Raghunandan, Rama ;

Lu, Hanxin ;

Zhou, Bin ;

Thomas, D. Nigel ;

Hickman, Somia P. ;

Kpamegan, Eloi ;

Boddapati, Sarathi ;

Piedra, Pedro A. .

VACCINE, 2013, 31 (03) :524-532

[9] What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? The Importance of Bridging Studies and Species-Independent Correlates of Protection [J].

Golding, Hana ;

Khurana, Surender ;

Zaitseva, Marina .

COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2018, 10 (04)

[10] Six-Month Safety Data of Recombinant Vesicular Stomatitis Virus-Zaire Ebola Virus Envelope Glycoprotein Vaccine in a Phase 3 Double-Blind, Placebo-Controlled Randomized Study in Healthy Adults [J].

Halperin, Scott A. ;

Arribas, Jose R. ;

Rupp, Richard ;

Andrews, Charles P. ;

Chu, Laurence ;

Das, Rituparna ;

Simon, Jakub K. ;

Onorato, Matthew T. ;

Liu, Kenneth ;

Martin, Jason ;

Helmond, Frans A. .

JOURNAL OF INFECTIOUS DISEASES, 2017, 215 (12) :1789-1798

← 1 2 3 →