Clinical trials with alum-adjuvanted formalin-inactivated human respiratory syncytial virus (FI-RSV) vaccine failed in children due to vaccine-enhanced disease upon RSV infection. In this study, we found that inactivated, detergent-split RSV vaccine (Split) displayed higher reactivity against neutralizing antibodies in vitro and less histopathology in primed adult mice after challenge, compared to FI-RSV. The immunogenicity and efficacy of FI-RSV and Split RSV vaccine were further determined in 2 weeks old mice after a single dose in the absence or presence of monophosphoryl lipid A (MPL) + CpG combination adjuvant. Split RSV with MPL + CpG adjuvant was effective in increasing T helper type 1 (Th1) immune responses and IgG2a isotype antibodies, neutralizing activity, and lung viral clearance as well as modulating immune responses to prevent pulmonary histopathology after RSV vaccination and challenge. This study demonstrates the efficacy of Split RSV as an effective vaccine candidate.
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This work was supported by National Institutes of Health / National Institute of Allergy and Infectious Diseases grants AI093772 , AI105170 , and AI134132 to SMK. The authors acknowledge the provision of RSV F purified proteins in post-fusion and pre-fusion conformation, and 5C4 monoclonal antibody from Dr. Barney S. Graham at Vaccine Research Center (NIAID, NIH, Bethesda, MD 20892, USA). The bacterial expression plasmid encoding RSV A2 G protein fragment (aa131-230) was kindly provided by Dr. MK Song and G protein fragment prepared by Drs. C Kim and JS Lee.
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