Lee Sujin, Nguyen Minh Trang, Currier Michael G, Jenkins Joe B, Strobert Elizabeth A, Kajon Adriana E, Madan-Lala Ranjna, Bochkov Yury A, Gern James E, Roy Krishnendu, Lu Xiaoyan, Erdman Dean D, Spearman Paul, Moore Martin L
Department of Pediatrics, Emory University, Atlanta, Georgia 30322, USA.
Children's Healthcare of Atlanta, Atlanta, Georgia 30322, USA.
Nat Commun. 2016 Sep 22;7:12838. doi: 10.1038/ncomms12838.
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.
作为普通感冒的主要病原体,人鼻病毒(HRV)是人类传染病的主要病因。早期研究表明,单价福尔马林灭活的HRV疫苗具有保护作用,且病毒中和抗体(nAb)与保护作用相关。然而,多种HRV类型的共同流行阻碍了进一步的疫苗研发工作。在此,我们检验了这样一种假设,即在多价灭活HRV疫苗中增加病毒输入滴度可能会引发广泛的nAb反应。我们发现,多价灭活HRV加氢氧化铝(明矾)佐剂可诱导针对多种鼻病毒类型的血清nAb。在小鼠中使用高达25价、在恒河猴中使用高达50价的制剂,HRV疫苗的免疫原性与输入抗原的足够数量相关,而价数不是反应效力或广度的主要因素。因此,我们研发出了一种能够诱导针对多种不同HRV类型产生nAb反应的疫苗。