50-valent inactivated rhinovirus vaccine is broadly immunogenic in rhesus macaques

As the predominant etiological agent of the common cold, human rhinovirus (HRV) is the leading cause of human infectious disease. Early studies showed 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. We approached this problem straightforwardly. We tested the hypothesis that increasing virus input titers in polyvalent inactivated HRV vaccine will result in broad nAb responses. Here, 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. We for the first time generated a vaccine capable of inducing nAb responses to numerous and diverse HRV types.