Academician I.N. Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology of Rospotrebnadzor (Russian Federal Consumer Rights Protection and Human Health Control Service), 603950, 71 M. Yamskay str., Nizhny Novgorod, Russia.
Academician I.N. Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology of Rospotrebnadzor (Russian Federal Consumer Rights Protection and Human Health Control Service), 603950, 71 M. Yamskay str., Nizhny Novgorod, Russia.
Vaccine. 2020 Sep 29;38(42):6645-6655. doi: 10.1016/j.vaccine.2020.07.053. Epub 2020 Aug 29.
The influenza vaccine Grippol® Quadrivalent (GQ) is a new vaccine, containing the adjuvant Polyoxidonium® and recombinant hemagglutinins from 4 strains of the influenza virus in amount of 5-6 μg of each hemagglutinin per human dose. These doses of antigens are about 3 times less than the standard dose recommended by WHO. We sought to characterize the immune response to the GQ vaccine and to determine the contribution of the adjuvant in this response. BALB/c mice were vaccinated with GQ or with adjuvant-free antigen mixtures (AGs). Then, the antibody response, the number of memory T cells in the spleen, and the functional properties of splenocytes were determined. The vaccine GQ has been shown to induce antibodies to all 4 influenza hemagglutinins. The vaccination with GQ caused a strong increase in the AG-induced proliferation and production of Th2 cytokines ex vivo. These effects were equal to effect achieved by standard dose of antigens. Vaccination also caused the accumulation of CD4 large lymphocytes with the phenotype of central and effector memory T cells in the spleen. The GQ vaccine enhanced the cytolytic activity of natural killer (NK) cells, whereas the adjuvant-free mixture of AGs in lowered and standard doses did not affect NK activity. We did not find a noticeable response of Th1 and CD8 T cells to vaccination. In vitro, the GQ vaccine stimulated the maturation of human monocyte-derived dendritic cells (DCs) enhancing the expression of HLA-DR, CD80, CD83, CD86 and ICOSL molecules. Polyoxidonium without AGs also induced expression of ICOSL, which plays an important role in T-dependent humoral immune response. In summary, the low-dose influenza vaccine GQ with Polyoxidonium adjuvant is immunogenic, induces a Th2-polarized T-cell response and CD4 memory T cells maturation, activates the production of antibodies to influenza hemagglutinins, and increases the activity of NK cells.
流感疫苗 Grippol® 四价疫苗（GQ）是一种新型疫苗，含有佐剂 Polyoxidonium®和来自 4 株流感病毒的重组血凝素，每人体剂量的每种血凝素为 5-6μg。这些抗原剂量约为世界卫生组织推荐标准剂量的 3 倍。我们试图描述 GQ 疫苗的免疫反应，并确定佐剂在这种反应中的作用。BALB/c 小鼠用 GQ 或无佐剂的抗原混合物（AGs）进行疫苗接种。然后，测定抗体反应、脾内记忆 T 细胞数量以及脾细胞的功能特性。结果表明，GQ 疫苗可诱导针对所有 4 种流感血凝素的抗体。与 GQ 疫苗接种相比，AG 诱导的脾细胞增殖和 Th2 细胞因子产生显著增加。这些效果与抗原标准剂量相当。接种疫苗还导致脾内 CD4 大淋巴细胞的积累，其表型为中央和效应记忆 T 细胞。GQ 疫苗增强了自然杀伤（NK）细胞的细胞溶解活性，而无佐剂的 AG 混合物在低剂量和标准剂量下均未影响 NK 活性。我们没有发现 Th1 和 CD8 T 细胞对疫苗接种有明显反应。在体外，GQ 疫苗刺激人单核细胞衍生树突状细胞（DCs）的成熟，增强 HLA-DR、CD80、CD83、CD86 和 ICOSL 分子的表达。无 AGs 的 Polyoxidonium 也诱导了 ICOSL 的表达，后者在 T 细胞依赖性体液免疫反应中起重要作用。总之，含有 Polyoxidonium 佐剂的低剂量流感疫苗 GQ 具有免疫原性，可诱导 Th2 极化的 T 细胞反应和 CD4 记忆 T 细胞成熟，激活针对流感血凝素的抗体产生，并增加 NK 细胞的活性。
