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

Sujin Lee; Minh Trang Nguyen; Michael G. Currier; Joe B. Jenkins; Elizabeth A. Strobert; Adriana E. Kajon; Ranjna Madan-Lala; Yury A. Bochkov; James E. Gern; Krishnendu Roy; Xiaoyan Lu; Dean D. Erdman; Paul Spearman; Martin L. Moore

HRV causes respiratory illness in billions of people annually, a socioeconomic burden 1 . 33 HRV also causes pneumonia hospitalizations in children and adults and exacerbations of asthma 34 and chronic obstructive pulmonary disease (COPD) 2 . HRV was found to be the second leading 35 cause of community-acquired pneumonia requiring hospitalization in US children, second only 36 to respiratory syncytial virus, and the most common pathogen associated with pneumonia 37 hospitalization in US adults 3,4 . A vaccine for HRV could alleviate serious disease in asthma and virus-neutralizing antibodies (nAb) as a correlate of protection, and estimated duration of 41 immunity 5-11 . Trials with monovalent HRV vaccine demonstrated that protection from 42 homologous challenge and disease can be achieved with formalin-inactivated virus given 43 intramuscularly (i.m.) or intranasally (i.n.) 8,10,11 . Humoral immunity to heterologous virus types 44 was not observed, though cross-reactive CD8 T cells can promote clearance 12, 13 . Limited cross- 45 neutralizing Abs can be induced by hyper-immunization in animals 14, 15 . The possibility of a 46 vaccine composed of 50, 100, or more distinct HRV antigens has been viewed as formidable or The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/053967 doi: bioRxiv preprint nAb in guinea pigs, and a reciprocal serum nAb titer of 2 3 resulting from four doses of a 1:125 64 dilution of the vaccine correlated with vaccine efficacy in humans 9 . Although the nAb titer 65 required for protection is not defined, early studies established inactivated HRV as protective in 66 humans, and immunogenicity in animals informed clinical testing.