EV-D68 virus-like particle vaccines elicit cross-clade neutralizing antibodies that inhibit infection and block dissemination

被引：19

作者：

Krug, Peter W. ^{[1
]}

Wang, Lingshu ^{[1
]}

Shi, Wei ^{[1
]}

Kong, Wing-Pui ^{[1
]}

Moss, Daniel L. ^{[1
]}

Yang, Eun Sung ^{[1
]}

Fisher, Brian E. ^{[1
]}

Morabito, Kaitlyn M. ^{[1
]}

Mascola, John R. ^{[1
,2
]}

Kanekiyo, Masaru ^{[1
]}

Graham, Barney S. ^{[1
,3
]}

Ruckwardt, Tracy J. ^{[1
]}

机构：

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

[2] ModeX Therapeut, Natick, MA 01760 USA

[3] Morehouse Sch Med, Dept Med & Microbiol Biochem & Immunol, Atlanta, GA 30310 USA

来源：

SCIENCE ADVANCES | 2023年 / 9卷 / 20期

基金：

美国国家卫生研究院;

关键词：

ACUTE FLACCID MYELITIS; ENTEROVIRUS D68; MOUTH-DISEASE; 2014; OUTBREAK; KANSAS-CITY; POLIOVIRUS; CHILDREN; IMMUNITY; CHALLENGE; EMERGENCE;

D O I：

10.1126/sciadv.adg6076

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：

Enterovirus D68 (EV-D68) causes severe respiratory illness in children and can result in a debilitating paralytic disease known as acute flaccid myelitis. No treatment or vaccine for EV-D68 infection is available. Here, we dem-onstrate that virus-like particle (VLP) vaccines elicit a protective neutralizing antibody against homologous and heterologous EV-D68 subclades. VLP based on a B1 subclade 2014 outbreak strain elicited comparable B1 EV-D68 neutralizing activity as an inactivated viral particle vaccine in mice. Both immunogens elicited weaker cross -neutralization against heterologous viruses. A B3 VLP vaccine elicited more robust neutralization of B3 subclade viruses with improved cross-neutralization. A balanced CD4+ T helper response was achieved using a carbomer-based adjuvant, Adjuplex. Nonhuman primates immunized with this B3 VLP Adjuplex formulation generated robust neutralizing antibodies against homologous and heterologous subclade viruses. Our results suggest that both vaccine strain and adjuvant selection are critical elements for improving the breadth of protective immu-nity against EV-D68.

引用

页数：14

共 62 条

[1] Mammalian expression of virus-like particles as a proof of principle for next generation polio vaccines [J].