Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5536703 | Vaccine | 2017 | 10 Pages |
Abstract
Vaccines are administered to healthy humans, including infants, so the safety and efficacy must be very high. Therefore, evaluating vaccine safety in preclinical and clinical studies, according to World Health Organization guidelines, is crucial for vaccine development and clinical use. A change in the route of administration is considered to alter a vaccine's immunogenicity. Several adjuvants have also been developed and approved for use in vaccines. However, the addition of adjuvants to vaccines may cause unwanted immune responses, including facial nerve paralysis and narcolepsy. Therefore, a more accurate and comprehensive strategy must be used to develope next-generation vaccines for ensuring vaccine safety. Previously, we have developed a system with which to evaluate vaccine safety in rats using a systematic vaccinological approach and 20 marker genes. In this study, we developed a safety evaluation system for nasally administered influenza vaccines and adjuvanted influenza vaccines using these marker genes. Expression of these genes increased dose-dependent manner when mice were intranasally administered the toxicity reference vaccine. When the adjuvant CpG K3 or a CpG-K3-combined influenza vaccine was administered intranasally, marker gene expression increased in a CpG-K3-dose-dependent way. A histopathological analysis indicated that marker gene expression correlated with vaccine- or adjuvant-induced phenotypic changes in the lung and nasal mucosa. We believe that the marker genes expression analyses will be useful in preclinical testing, adjuvant development, and selecting the appropriate dose of adjuvant in nasal administration vaccines.
Keywords
diphtheria–tetanus–pertussiswpvWBCHAVLTTTLRQGPDPTMPONALTAbnormal toxicity testAdjuvantinterferonIFNNasal-associated lymphoid tissueATTSafety testToll-like receptorJEVphysiological salinemyeloperoxidaseHematoxylin and Eosinhemagglutinininfluenza vaccineNasal vaccineJapanese encephalitis virusMarker genewhite blood cells
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Authors
Eita Sasaki, Madoka Kuramitsu, Haruka Momose, Kouji Kobiyama, Taiki Aoshi, Hiroshi Yamada, Ken J. Ishii, Takuo Mizukami, Isao Hamaguchi,