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

In 1975, it was reported that two different 10-valent inactivated HRV preparations 83 induced nAb titers to only 30-40% of the input virus types in recipient subjects 33 . However, the 84 input titers of viruses prior to inactivation ranged from 10 1.5 to 10 5.5 TCID 50 per ml, and these 85 were then diluted 10-fold to generate 10-valent 1.0 ml doses given i.m. as prime and boost with 86 . CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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 no adjuvant 33 . We hypothesized that low input antigen doses are responsible for poor nAb 87 responses to 10-valent inactivated HRV. We reconstituted the 1975 10-valent vaccine, as closely 88 as possible with available HRV types, over a 10 1 to 10 5 inactivated-TCID 50 per vaccine dose, and 89 we compared it to a 10-valent vaccine of the same types with input titers ranging from > 10 5 to > 90 10 7 inactivated-TCID 50 per dose. The reconstituted 1975 vaccine resulted in no detectable nAb 91 after prime vaccination and, following boost vaccination, nAb to the five types that had the 92 highest input titers (Fig. 2) . The high titer vaccine resulted in nAb to 5 of 10 types after prime 93 vaccination and all 10 types after the boost (Fig. 2) . Following the boost vaccinations, there 94 appeared to be a 10 4 inactivated-TCID 50 per vaccine dose threshold for the induction of nAb in 95 this model (Fig. 2b) . Above this titer, there was no correlation between input load and nAb Table 2 ) to accommodate the volume adjustment. The 10-valent inactivated 102 HRV vaccine induced nAb to 100% of input types following the prime and the boost (Fig. 3a) . 103 The nAb induced by 10-valent inactivated HRV were persisting at 203 days post-boost 104 (Supplemental Fig. 2) . The 25-valent inactivated HRV prime vaccination induced nAb to 18 of 105 25 (72%) virus types, and the 25-valent boost resulted in nAb against 24 of the 25 types (96%) 106 (Fig 3b) . The average nAb titer resulting from prime + boost was 2 7 for 10-valent and 2 6.8 for 25-107 valent. The data demonstrate broad neutralization of diverse HRV types with a straightforward 108 vaccine approach.