A virus-like particle vaccine prevents equine encephalitis virus infection in nonhuman primates

被引：48

作者：

Ko, Sung-Youl ^{[1
]}

Akahata, Wataru ^{[1
,9
]}

Yang, Eun Sung ^{[1
]}

Kong, Wing-Pui ^{[1
]}

Burke, Crystal W. ^{[2
]}

Honnold, Shelley P. ^{[3
]}

Nichols, Donald K. ^{[3
]}

Huang, Yan-Jang S. ^{[4
,5
]}

Schieber, Gretchen L. ^{[1
,10
]}

Carlton, Kevin ^{[1
]}

DaSilva, Luis ^{[6
]}

Traina-Dorge, Vicki ^{[7
]}

Vanlandingham, Dana L. ^{[4
,5
]}

Tsybovsky, Yaroslav ^{[8
]}

Stephens, Tyler ^{[8
]}

Baxa, Ulrich ^{[8
]}

Higgs, Stephen ^{[4
,5
]}

Roy, Chad J. ^{[7
]}

Glass, Pamela J. ^{[2
]}

Mascola, John R. ^{[1
]}

Nabel, Gary J. ^{[1
,11
]}

Rao, Srinivas S. ^{[1
,11
]}

机构：

[1] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[2] USAMRIID, Virol Div, Frederick, MD 21702 USA

[3] USAMRIID, Pathol Div, Frederick, MD 21702 USA

[4] Kansas State Univ, Coll Vet Med, Biosecur Res Inst, Manhattan, KS 66506 USA

[5] Kansas State Univ, Coll Vet Med, Dept Diagnost Med Pathobiol, Manhattan, KS 66506 USA

[6] USAMRIID, Ctr Aerobiolo Sci, Frederick, MD 21702 USA

[7] Tulane Natl Primate Res Ctr, Div Microbiol, Covington, LA 70433 USA

[8] NCI, Electron Microscopy Lab, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA

[9] VLP Therapeut, 19 Firstfield Rd, Gaithersburg, MD 20878 USA

[10] NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[11] Sanofi, 640 Mem Dr, Cambridge, MA 02139 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2019年 / 11卷 / 492期

关键词：

EASTERN EQUINE; NEUTRALIZING ANTIBODIES; INTRANASAL CHALLENGE; ALPHAVIRUS VACCINE; IMMUNE-RESPONSES; DNA VACCINE; MICE; PROTECTS; IMMUNIZATION; REPLICATION;

D O I：

10.1126/scitranslmed.aav3113

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Western, Eastern, and Venezuelan equine encephalitis viruses (WEEV, EEEV, and VEEV, respectively) are important mosquito-borne agents that pose public health and bioterrorism threats. Despite considerable advances in understanding alphavirus replication, there are currently no available effective vaccines or antiviral treatments against these highly lethal pathogens. To develop a potential countermeasure for viral encephalitis, we generated a trivalent, or three-component, EEV vaccine composed of virus-like particles (VLPs). Monovalent VLPs elicited neutralizing antibody responses and protected mice and nonhuman primates (NHPs) against homologous challenges, but they were not cross-protective. In contrast, NHPs immunized with trivalent VLPs were completely protected against aerosol challenge by each of these three EEVs. Passive transfer of IgG from immunized NHPs protected mice against aerosolized EEV challenge, demonstrating that the mechanism of protection was humoral. Because they are replication incompetent, these trivalent VLPs represent a potentially safe and effective vaccine that can protect against diverse encephalitis viruses.

引用

页数：12

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