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

Results and discussion 69 We first used BALB/c mice to test immunogenicity. We propagated HRVs in H1-HeLa 70 cells and inactivated infectivity using formalin. Sera from naïve mice had no detectable nAb 71 against HRV-16 ( Fig. 1) . Alum adjuvant enhanced the nAb response induced by i.m. inactivated 72 HRV-16 ( Fig. 1) . There was no effect of valency (comparing 1-, 3-, 5-, 7-, and 10-valent) on the 73 nAb response induced by inactivated HRV-16 or to the 3 types in the 3-valent vaccine (HRV-16, 74 HRV-36, and HRV-78) (Fig. 1) . The 50% tissue culture infectious dose (TCID 50 ) titers of the 75 input viruses prior to inactivation (inactivated-TCID 50 ) are provided in Supplemental Table 1 . 76 Original antigenic sin can occur when sequential exposure to related virus variants results in 77 biased immunity to the type encountered first 32 . In bivalent HRV-immune mice, we observed 78 modest original antigenic sin following prime vaccination with 10-valent inactivated HRV, and 79 boost vaccination partially alleviated the effect (Supplemental Fig. 1) , similar to influenza 80 virus 32 . Collectively, these results prompted us to explore more fully the nAb response to 81 polyvalent HRV vaccine.