Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
Curr Med Chem. 2023;30(26):3024-3031. doi: 10.2174/0929867329666220930114429.
To evaluate the immunogenic potential of the carrier-free peptide-based anti-PCSK9 (proprotein convertase subtilisin/kexin 9) vaccine in albino mice.
The immunogenic pcsk9 peptide and 0.4% alum adjuvant were mixed thoroughly at a 1:1 ratio and used as a vaccine formulation. To assess the humoral immune response, animals' blood was sampled two weeks after the last immunization. The ELISA method was employed to measure serum anti-PCSK9 antibody titers, PCSK9 concentrations, and PCSK9/LDLR interaction.
ELISA analysis showed significant induction of IgG antibody titers by PCSK9 peptide vaccine in vaccinated mice sera compared to the control mice (in male and female mice were 12000±586 and 11566±642, respectively, p<0.001). Mechanistic analyses showed a significant reduction in serum PCSK9 concentrations by vaccine-induced antibodies in vaccine groups compared to the control groups (in male mice by 29±5 ng/mL (22.4%), p<0.001 and female mice by 26±5 ng / mL (21.0%), p<0.001). Serum concentrations of PCSK9 in control and vaccine groups were 131±8.6 ng / mL and 102±8.1 ng/ml in male mice and 124±6 ng/ml and 98±10 ng/ml in female mice, respectively. Moreover, vaccine-induced antibodies inhibited the PCSK9-LDLR interaction in male and female groups by 34% and 26%, respectively. No significant difference was detected between the male and female groups in all tests (p>0.05).
According to our results, the PCSK9 peptide vaccine provoked the humoral immune system in albino mice to produce functional antibodies that inhibit plasma PCSK9. These effects were seen in both genders without any significant difference.
评估无载体肽基抗 PCSK9（前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9）疫苗在白化小鼠中的免疫原性。
将免疫原性 pcsk9 肽和 0.4%的明矾佐剂按 1:1 的比例充分混合，作为疫苗制剂。为了评估体液免疫反应，在最后一次免疫后两周采集动物的血液。采用 ELISA 法检测血清抗 PCSK9 抗体滴度、PCSK9 浓度和 PCSK9/LDLR 相互作用。
ELISA 分析显示，与对照组相比，PCSK9 肽疫苗在接种小鼠血清中显著诱导 IgG 抗体滴度升高（雄性和雌性小鼠分别为 12000±586 和 11566±642，p<0.001）。机制分析显示，疫苗诱导的抗体使疫苗组血清 PCSK9 浓度显著降低，与对照组相比（雄性小鼠降低 29±5ng/mL（22.4%），p<0.001，雌性小鼠降低 26±5ng/mL（21.0%），p<0.001）。对照组和疫苗组的血清 PCSK9 浓度分别为雄性小鼠 131±8.6ng/mL 和 102±8.1ng/ml，雌性小鼠 124±6ng/ml 和 98±10ng/ml。此外，疫苗诱导的抗体分别抑制了雄性和雌性小鼠中 34%和 26%的 PCSK9-LDLR 相互作用。在所有测试中，雄性和雌性组之间均未检测到显著差异（p>0.05）。
根据我们的结果，PCSK9 肽疫苗激发了白化小鼠的体液免疫系统产生功能性抗体，抑制了血浆 PCSK9。这些作用在两性中均可见，且无显著差异。
