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

Following boost vaccination, there were serum nAb titers against 100% of the types in 25-valent 120 HRV-vaccinated RMs (Fig. 4b) and 98% (49 out of 50) of the virus types in 50-valent HRV-121 vaccinated RMs (Fig. 4d) . The average nAb titer resulting from prime + boost in RMs was 2 9.3 122 for 25-valent and 2 8.6 for 50-valent. The nAb responses were type-specific, not cross- The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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 production. Adequate yields were obtained from WI-38 cells (Supplemental Fig. 4) . Injectable 133 vaccines require defined purity. As proof of principle, we purified three HRV types by high 134 performance liquid chromatography and found uncompromised immunogenicity of trivalent 135 inactivated purified HRV in mice (Supplemental Fig. 5) . 136 Forty years ago, the prospects for a polyvalent HRV vaccine were dour for good Advancing valency may be applicable to vaccines for other antigenically variable pathogens. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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 tapered microtip secured on a ring stand. Sonication was performed by an operator in a closed 179 room with ear protection, at 10 % amplitude, 1 sec on/1 sec off intervals, and 1 pulse per 1 ml of 180 material. Sonication yielded higher titers than freeze-thaw. The suspension was clarified by 181 centrifugation at 931 × g for 10 minutes. The supernatant was transferred to cryovials, snap- The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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 (10 mg/kg) or Telazol (4 mg/kg) anesthesia on fasting animals. Following anesthesia with 248 ketamine or Telazol, the animals were bled from the femoral vein. Yerkes blood collection 249 guidelines were followed and no more than 10 ml/kg/28 days of blood was collected. After for each group, and nAb titers (y-axis) were measured against the indicated types in the vaccines.