A polyvalent inactivated rhinovirus vaccine is broadly immunogenic in rhesus macaques

被引:40
作者
Lee, Sujin [1 ,2 ]
Minh Trang Nguyen [1 ,2 ]
Currier, Michael G. [1 ,2 ]
Jenkins, Joe B. [3 ]
Strobert, Elizabeth A. [3 ]
Kajon, Adriana E. [4 ]
Madan-Lala, Ranjna [5 ]
Bochkov, Yury A. [6 ]
Gern, James E. [6 ,7 ]
Roy, Krishnendu [5 ]
Lu, Xiaoyan [8 ]
Erdman, Dean D. [8 ]
Spearman, Paul [1 ,2 ]
Moore, Martin L. [1 ,2 ]
机构
[1] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA
[2] Childrens Healthcare Atlanta, Atlanta, GA 30322 USA
[3] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA
[4] Lovelace Resp Res Inst, Program Infect Dis, Albuquerque, NM 87108 USA
[5] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA
[6] Univ Wisconsin, Dept Pediat, Madison, WI 53792 USA
[7] Univ Wisconsin, Dept Med, Madison, WI 53792 USA
[8] Ctr Dis Control & Prevent, Div Viral Dis, Atlanta, GA 30333 USA
基金
美国国家卫生研究院;
关键词
PNEUMONIA REQUIRING HOSPITALIZATION; RESPIRATORY-TRACT INFECTIONS; NEUTRALIZING ANTIBODY; ILLNESS; RESPONSES; STRATEGIES; GENOTYPE; CHILDREN; ADULTS;
D O I
10.1038/ncomms12838
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
As the predominant aetiological agent of the common cold, human rhinovirus (HRV) is the leading cause of human infectious disease. Early studies showed that a monovalent formalin-inactivated HRV vaccine can be protective, and virus-neutralizing antibodies (nAb) correlated with protection. However, co-circulation of many HRV types discouraged further vaccine efforts. Here, we test the hypothesis that increasing virus input titres in polyvalent inactivated HRV vaccine may result in broad nAb responses. We show that serum nAb against many rhinovirus types can be induced by polyvalent, inactivated HRVs plus alhydrogel (alum) adjuvant. Using formulations up to 25-valent in mice and 50-valent in rhesus macaques, HRV vaccine immunogenicity was related to sufficient quantity of input antigens, and valency was not a major factor for potency or breadth of the response. Thus, we have generated a vaccine capable of inducing nAb responses to numerous and diverse HRV types.
引用
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页数:7
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