title: Assessment of the protective effect of Imvamune and Acam2000 vaccines against aerosolized monkeypox virus in cynomolgus macaques.
abstract: To support the licensure of a new and safer vaccine to protect people against smallpox, a monkeypox model of infection in cynomolgus macaques, which simulates smallpox in humans, was used to evaluate two vaccines, Acam2000 and Imvamune, for protection against disease. Animals vaccinated with a single immunization of Imvamune were not protected completely from severe and/or lethal infection, whereas those receiving either a prime and boost of Imvamune or a single immunization with Acam2000 were protected completely. Additional parameters, including clinical observations, radiographs, viral load in blood, throat swabs, and selected tissues, vaccinia virus-specific antibody responses, immunophenotyping, extracellular cytokine levels, and histopathology were assessed. There was no significant difference (P > 0.05) between the levels of neutralizing antibody in animals vaccinated with a single immunization of Acam2000 (132 U/ml) and the prime-boost Imvamune regime (69 U/ml) prior to challenge with monkeypox virus. After challenge, there was evidence of viral excretion from the throats of 2 of 6 animals in the prime-boost Imvamune group, whereas there was no confirmation of excreted live virus in the Acam2000 group. This evaluation of different human smallpox vaccines in cynomolgus macaques helps to provide information about optimal vaccine strategies in the absence of human challenge studies.
authors: Microbiological Services, Public Health England, Salisbury, Wiltshire, United Kingdom. graham.hatch@phe.gov.uk
authors: Graham J
authors: GJ
authors: Hatch
authors: Victoria A
authors: VA
authors: Graham
authors: Kevin R
authors: KR
authors: Bewley
authors: Julia A
authors: JA
authors: Tree
authors: Mike
authors: M
authors: Dennis
authors: Irene
authors: I
authors: Taylor
authors: Simon G P
authors: SG
authors: Funnell
authors: Simon R
authors: SR
authors: Bate
authors: Kimberley
authors: K
authors: Steeds
authors: Thomas
authors: T
authors: Tipton
authors: Thomas
authors: T
authors: Bean
authors: Laura
authors: L
authors: Hudson
authors: Deborah J
authors: DJ
authors: Atkinson
authors: Gemma
authors: G
authors: McLuckie
authors: Melanie
authors: M
authors: Charlwood
authors: Allen D G
authors: AD
authors: Roberts
authors: Julia
authors: J
authors: Vipond
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D057134:Antibodies, Neutralizing / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007114:Immunization / Q000379:methods; D008252:Macaca fascicularis; D060888:Real-Time Polymerase Chain Reaction; D012900:Smallpox Vaccine / Q000494:pharmacology; D014613:Vaccines, Attenuated / Q000494:pharmacology; D017201:Virus Shedding / Q000276:immunology; D045908:Mpox, Monkeypox / Q000517:prevention & control; D008993:Monkeypox virus / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; C527606:smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic; D012900:Smallpox Vaccine; D014613:Vaccines, Attenuated
references: J Virol. 2011 Sep;85(18):9527-42
references: 21752919
references: Expert Rev Vaccines. 2009 Jan;8(1):13-24
references: 19093767
references: Trends Microbiol. 2012 Feb;20(2):80-7
references: 22239910
references: J Infect Dis. 2011 Jan 1;203(1):95-102
references: 21148501
references: Eff Clin Pract. 2002 Mar-Apr;5(2):84-90
references: 11990216
references: Dtsch Med Wochenschr. 1974 Nov 22;99(47):2386-92
references: 4426258
references: Vaccine. 2010 Sep 14;28(40):6627-36
references: 20659519
references: J Hyg (Lond). 1969 Sep;67(3):437-48
references: 5258223
references: PLoS One. 2012;7(7):e42353
references: 22860117
references: Clin Infect Dis. 2003 Mar 15;36(6):766-74
references: 12627361
references: Antimicrob Agents Chemother. 2009 Jun;53(6):2620-5
references: 19349521
references: J Trop Med Hyg. 1987 Feb;90(1):31-8
references: 3029395
references: Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16262-7
references: 20805472
references: Zoonoses Public Health. 2010 Dec;57(7-8):e149-55
references: 20042058
references: Vaccine. 2010 Feb 3;28(5):1209-16
references: 19944151
references: Nature. 2004 Mar 11;428(6979):182-5
references: 15014500
references: Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004913
references: 17636779
references: Antimicrob Agents Chemother. 2009 May;53(5):1817-22
references: 19223621
references: Emerg Infect Dis. 2001 May-Jun;7(3):434-8
references: 11384521
references: Comp Immunol Microbiol Infect Dis. 2003 Oct;26(5-6):423-30
references: 12818626
references: Vaccine. 2011 Dec 6;29(52):9684-90
references: 22001879
references: PLoS One. 2010 Dec 30;5(12):e15547
references: 21209900
references: J Comp Pathol. 2013 Jan;148(1):6-21
references: 22884034
references: Expert Opin Investig Drugs. 2008 Apr;17(4):555-64
references: 18363519
references: J Virol. 2011 Aug;85(15):7683-98
references: 21632764
references: J Clin Microbiol. 2002 Aug;40(8):2919-21
references: 12149352
references: Vaccine. 2010 Oct 8;28(43):7081-91
references: 20728526
references: J Virol. 2005 Jun;79(12):7845-51
references: 15919938
references: Vaccine. 2009 Sep 4;27(40):5496-504
references: 19632316
references: Antiviral Res. 2009 Oct;84(1):1-13
references: 19563829
references: Emerg Infect Dis. 2007 Jul;13(7):965-72
references: 18214166
references: Fed Regist. 2002 May 31;67(105):37988-98
references: 12049094
references: Vet Pathol. 2010 Sep;47(5):852-70
references: 20682806
references: Front Cell Infect Microbiol. 2012 Sep 17;2:117
references: 23061051
references: J Virol. 2009 Nov;83(22):11959-65
references: 19740988
references: Lancet Infect Dis. 2010 Apr;10(4):288
references: 20334852
references: Vaccine. 2011 Dec 30;29 Suppl 4:D60-4
references: 22188935
references: J Virol. 2011 May;85(10):4898-909
references: 21389129
references: Int J Infect Dis. 2004 Oct;8 Suppl 2:S31-44
references: 15491873
references: Vaccine. 2007 Dec 12;25(51):8562-73
references: 18036708
references: Lab Invest. 2001 Dec;81(12):1581-600
references: 11742030
references: Zentralbl Bakteriol B. 1978 Dec;167(5-6):375-90
references: 219640
references: PLoS One. 2010 Sep 20;5(9):
references: 20862223
references: Eur J Toxicol Environ Hyg. 1974 Mar-Apr;7(2):77-84
references: 4408718