Kwak Hye Won, Shin Wooseok, Baik Kyunghwa, Kim Minsun, Park YongWook, Hong So-Hee, Park Hyo-Jung, Park Hyeong-Jun, Bang Yoo-Jin, Kim Jae-Yong, Lee Yu-Sun, Kim In-Beom, Kim Hong-Lim, Kim Hun, Nam Jae-Hwan
Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, Republic of Korea.
Department of R&D, SMLbiopharm, Bucheon, Republic of Korea.
Microbiol Immunol. 2022 Nov;66(11):529-537. doi: 10.1111/1348-0421.13024. Epub 2022 Sep 5.
Following the development of various types of vaccines, the use of adjuvants to boost vaccine efficacy has become a focus of research. Aluminum hydroxide (alum), the most commonly used adjuvant, induces a certain immune response and ensures safety in human trials. However, alum mainly induces only a Th2 response; its Th1 response is weak. Thus, we previously developed a single-stranded ribose nucleic acid (ssRNA) adjuvant that induces a Th1 response through toll-like receptors. Here, we explored whether 10-valent human papilloma virus (HPV)-like particle (VLP) vaccine formulated with ssRNA adjuvant and alum helped to enhance immune response and maintained memory response. The mice were immunized intramuscularly twice at 2 week intervals and were inoculated 4 days after the second boost (after about 1 year). The antibody response and T cell activation were measured by Elispot, ELISA using harvested serum and splenocytes. The 10-valent HPV VLP vaccine formulated with ssRNA adjuvant and alum increased the antigen-specific immune response more than alum used alone. It increased each type-specific IgG1/IgG2a titer, and antigen-specific IFN-γ cells. Furthermore, the ssRNA adjuvant with alum induced memory response. In memory response, each type-specific IgG1/IgG2c, IFN-γ, and IL-6 cytokine, and neutralizing antibodies were increased by the ssRNA adjuvant with alum. Overall, the ssRNA adjuvant with alum induced memory responses and balanced Th1/Th2 responses. The ssRNA adjuvant and alum may help to enhance prophylactic vaccine efficacy.
随着各类疫苗的研发,使用佐剂来提高疫苗效力已成为研究热点。氢氧化铝(明矾)是最常用的佐剂,能诱导一定的免疫反应并确保人体试验的安全性。然而,明矾主要仅诱导Th2反应,其Th1反应较弱。因此,我们之前开发了一种通过Toll样受体诱导Th1反应的单链核糖核酸(ssRNA)佐剂。在此,我们探究了用ssRNA佐剂和明矾配制的10价人乳头瘤病毒(HPV)样颗粒(VLP)疫苗是否有助于增强免疫反应并维持记忆反应。小鼠每隔2周进行两次肌肉注射免疫,并在第二次加强免疫后4天(约1年后)接种。通过酶联免疫斑点法(Elispot)、使用收获的血清和脾细胞的酶联免疫吸附测定法(ELISA)来测量抗体反应和T细胞活化。用ssRNA佐剂和明矾配制的10价HPV VLP疫苗比单独使用明矾更能增强抗原特异性免疫反应。它提高了每种类型特异性IgG1/IgG2a滴度以及抗原特异性干扰素-γ细胞。此外,含明矾的ssRNA佐剂诱导了记忆反应。在记忆反应中,含明矾的ssRNA佐剂使每种类型特异性IgG1/IgG2c、干扰素-γ和白细胞介素-6细胞因子以及中和抗体增加。总体而言,含明矾的ssRNA佐剂诱导了记忆反应并平衡了Th1/Th2反应。ssRNA佐剂和明矾可能有助于提高预防性疫苗的效力。