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评价单磷酰脂质 A 作为佐剂用于灭活的基孔肯雅病毒。

Evaluation of monophosphoryl lipid A as an adjuvanted for inactivated chikungunya virus.

机构信息

Department of Communicable Diseases, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Katraj-Dhankawadi, Pune-411043, India.

Department of Communicable Diseases, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Katraj-Dhankawadi, Pune-411043, India.

出版信息

Vaccine. 2022 Aug 12;40(34):5060-5068. doi: 10.1016/j.vaccine.2022.07.018. Epub 2022 Jul 21.

Abstract

Currently there is no clinically approved chikungunya virus (CHIKV) vaccine for immunization. Though definite need is felt, long disappearance of CHIKV has been a concern. Inactivated CHIKV (I-CHIKV) is an attractive antigen to develop effective vaccines within a short period of time. However, highly purified inactivated CHIKV do not contain necessary triggers for induction of robust antibody response. Monophosphoryl lipid A (MPLA) is a TLR4 ligand which is expressed on immune cells and is known to enhance immune response. Additionally, route of delivery also plays a critical role in modulating the immune response. Thus, antigen, adjuvant and route of delivery might modulate immune response if combined. Therefore in this study, we explored the immunogenicity of inactivated CHIKV-MPLA combination in mice after administration by intradermal or intramuscular route. Long term immune response study was also conducted by varying the antigen concentration and keeping the adjuvant concentration constant. Our study showed that the CHIKV-MPLA combination induced higher binding antibodies as well as neutralizing antibody titers as compared to unadjuvanted CHIKV. No difference in antibody titers was observed after delivery by either of the routes. However, difference in IFNγ and IL4 profiles was observed when a supernatant from stimulated splenocytes was analyzed. Taken together, these data show that both routes could be used for administration of the I-CHIKV-MPLA combination.

摘要

目前尚无经临床批准可用于免疫接种的基孔肯雅病毒 (CHIKV) 疫苗。尽管人们确实有这种需求,但 CHIKV 的长期消失一直令人担忧。灭活的 CHIKV(I-CHIKV)是一种有吸引力的抗原,可以在短时间内开发出有效的疫苗。然而,高度纯化的灭活 CHIKV 不含诱导强大抗体反应所需的必要触发因素。单磷酰脂质 A(MPLA)是一种 TLR4 配体,存在于免疫细胞上,已知可增强免疫反应。此外,给药途径在调节免疫反应方面也起着关键作用。因此,如果将抗原、佐剂和给药途径结合使用,可能会调节免疫反应。因此,在这项研究中,我们探索了经皮或肌肉内给药后,灭活的 CHIKV-MPLA 组合在小鼠中的免疫原性。通过改变抗原浓度并保持佐剂浓度不变,还进行了长期免疫反应研究。我们的研究表明,与未佐剂化的 CHIKV 相比,CHIKV-MPLA 组合诱导了更高的结合抗体和中和抗体滴度。两种途径给药后,抗体滴度没有差异。然而,当分析刺激脾细胞的上清液时,观察到 IFNγ 和 IL4 谱存在差异。总之,这些数据表明,两种途径均可用于给予 I-CHIKV-MPLA 组合。

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