Gebre Makda S, Rauch Susanne, Roth Nicole, Gergen Janina, Yu Jingyou, Liu Xiaowen, Cole Andrew C, Mueller Stefan O, Petsch Benjamin, Barouch Dan H
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
CureVac AG, Tübingen, Germany.
NPJ Vaccines. 2022 Aug 1;7(1):88. doi: 10.1038/s41541-022-00511-y.
mRNA vaccines can be developed and produced quickly, making them prime candidates for immediate outbreak responses. Furthermore, clinical trials have demonstrated rapid protection following mRNA vaccination. Thus, we sought to investigate how quickly mRNA vaccines elicit antibody responses compared to other vaccine modalities. We first compared the immune kinetics of mRNA and DNA vaccines expressing SARS-CoV-2 spike in mice. We observed rapid induction of antigen-specific binding and neutralizing antibodies by day 5 following mRNA (4 µg/mouse), but not DNA (50 µg/mouse), immunization. Comparing innate responses hours post immunization, the mRNA vaccine induced increased levels of IL-5, IL-6, and MCP-1 cytokines which maybe promoting humoral responses downstream. We then evaluated the immune kinetics of an HIV-1 mRNA vaccine in comparison to DNA, protein, and rhesus adenovirus 52 (RhAd52) vaccines of the same HIV-1 envelope antigen in mice. Again, induction of envelope-specific antibodies was observed by day 5 following mRNA vaccination, whereas antibodies were detected by day 7-14 following DNA, protein, and RhAd52 vaccination. Thus, eliciting rapid humoral immunity may be a unique and advantageous property of mRNA vaccines for controlling infectious disease outbreaks.
信使核糖核酸(mRNA)疫苗能够快速研发和生产,使其成为应对突发疫情的首选。此外,临床试验已证明接种mRNA疫苗后能迅速产生保护作用。因此,我们试图研究与其他疫苗类型相比,mRNA疫苗引发抗体反应的速度有多快。我们首先比较了在小鼠中表达严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突蛋白的mRNA疫苗和DNA疫苗的免疫动力学。我们观察到,在接种mRNA(4微克/小鼠)后第5天,抗原特异性结合抗体和中和抗体迅速诱导产生,但接种DNA(50微克/小鼠)后则未出现这种情况。在免疫后数小时比较先天免疫反应,mRNA疫苗诱导白细胞介素-5(IL-5)、白细胞介素-6(IL-6)和单核细胞趋化蛋白-1(MCP-1)细胞因子水平升高,这可能会促进下游的体液免疫反应。然后,我们评估了一种HIV-1 mRNA疫苗与相同HIV-1包膜抗原的DNA疫苗、蛋白质疫苗和恒河猴腺病毒52(RhAd52)疫苗在小鼠中的免疫动力学。同样,在接种mRNA疫苗后第5天观察到包膜特异性抗体的诱导产生,而在接种DNA疫苗、蛋白质疫苗和RhAd52疫苗后第7至14天检测到抗体。因此,引发快速体液免疫可能是mRNA疫苗在控制传染病暴发方面的独特且有利的特性。