RIG-I and TLR-7/8 agonists as combination adjuvant shapes unique antibody and cellular vaccine responses to seasonal influenza vaccine.
RIG-I and TLR-7/8 agonists as combination adjuvant shapes unique antibody and cellular vaccine responses to seasonal influenza vaccine.
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DOI：
10.3389/fimmu.2022.974016
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发表时间：
2022
影响因子：
7.3
通讯作者：
Schotsaert M
中科院分区：
文献类型：
--
作者：
Jangra S;Laghlali G;Choi A;Rathnasinghe R;Chen Y;Yildiz S;Coughlan L;García-Sastre A;De Geest BG;Schotsaert M
流感疫苗的有效性可以通过与一种有可能在数量和质量上增强宿主-疫苗反应的佐剂联合使用来提高。本研究的目的是探索rig - 1激动剂（sdi -纳米凝胶）和TLR7/8激动剂（Imidazoquinoline （IMDQ）‐PEG‐Chol）作为佐剂与许可的四价灭活流感疫苗（QIV）共同使用，并确定这些佐剂在指导辅助性T （Th）细胞反应中的作用，以及它们在免疫球蛋白（Ig）类转换中的作用。通过IFN-γ和IL-4酶联免疫吸附斑点（ELISPOT）检测，两种佐剂单独或联合使用QIV可增强BALB/c小鼠接种后4周的ha特异性血清ELISA IgG滴度、血清血凝抑制（HAI）滴度和脾T细胞反应。虽然QIV+ sdi纳米凝胶在很大程度上诱导了抗原特异性IgG1反应，但QIV+IMDQ-PEG-Chol主要诱导了IgG2a抗体同型，这表明它们分别有效诱导了Th2 （IL-4）和Th1 （IFN-γ）反应。两种佐剂的联合使用不仅使应答完全偏向IgG2a，而且还导致HAI滴度的诱导优于接受单一佐剂的组。此外，增强的IgG2a滴度与抗体介导的细胞毒性（ADCC）相关，ADCC针对高度保守的H1血凝（HA）茎结构域和N1神经氨酸酶（NA）。用QIV+IMDQ-PEG-Chol加强疫苗接种后，在接种QIV+IMDQ-PEG-Chol的动物中，IgG1/IgG2a的应答更加平衡，但在初级疫苗接种期间接受联合佐剂的动物中，IgG2a滴度仅增加，这表明初级疫苗接种期间生发中心的类转换事件有助于加强疫苗接种的结果。重要的是，IMDQ-PEG-Chol单独或联合使用的效果总是优于水包油控制佐剂Addavax。疫苗诱导的抗体和T细胞反应与预防致命流感病毒感染相关。这项研究详细说明佐剂的好处，靶向多种先天免疫受体塑造宿主疫苗反应。
Influenza vaccine effectiveness could be improved by combination with an adjuvant with the potential to enhance the host-vaccine response both quantitatively and qualitatively. The goal of this study was to explore a RIG-I agonist (SDI-nanogel) and a TLR7/8 agonist (Imidazoquinoline (IMDQ)‐PEG‐Chol) as adjuvants, when co-administered with a licensed quadrivalent inactivated influenza vaccine (QIV), and to determine the role of these adjuvants in directing helper T (Th) cell responses for their role in the immunoglobulin (Ig) class switching. Administration of QIV with the two adjuvants, individually or combined, resulted in enhanced HA-specific serum ELISA IgG titers, serum hemagglutination inhibition (HAI) titers and splenic T cell responses as examined by IFN-γ and IL-4 enzyme-linked immunosorbent spot (ELISPOT) assays, 4-weeks post-prime and post-boost vaccination in BALB/c mice. While QIV+SDI-nanogel largely induced antigen-specific IgG1 responses, QIV+IMDQ-PEG-Chol predominantly induced IgG2a antibody isotypes post-prime vaccination, suggesting efficient induction of Th2 (IL-4) and Th1 (IFN-γ) responses, respectively. Combination of the two adjuvants not only skewed the response completely towards IgG2a, but also resulted in induction of HAI titers that outperformed groups that received single adjuvant. Moreover, enhanced IgG2a titers correlate with antibody-mediated cellular cytotoxicity (ADCC) that targets both the highly conserved H1 hemagglutination (HA) stalk domain and N1 neuraminidase (NA). A booster vaccination with QIV+IMDQ-PEG-Chol resulted in a more balanced IgG1/IgG2a response in animals primed with QIV+IMDQ-PEG-Chol but increased only IgG2a titers in animals that received the combination adjuvant during prime vaccination, suggesting that class switching events in germinal centers during the prime vaccination contribute to the outcome of booster vaccination. Importantly, IMDQ-PEG-Chol, alone or in combination, always outperformed the oil-in-water control adjuvant Addavax. Vaccine-induced antibody and T cell responses correlated with protection against lethal influenza virus infection. This study details the benefit of adjuvants that target multiple innate immune receptors to shape the host vaccine response.
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DOI：
10.1084/jem.168.6.2373
发表时间：
1988-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Coutelier JP;van der Logt JT;Heessen FW;Vink A;van Snick J
通讯作者：
van Snick J
影响因子：
16.6
作者：
Jangra, Sonia;De Vrieze, Jana;Schotsaert, Michael
通讯作者：
Schotsaert, Michael
影响因子：
6.2
作者：
Lapi, Francesco;Marconi, Ettore;Cricelli, Claudio
通讯作者：
Cricelli, Claudio
影响因子：
5.5
作者：
Chromikova, Veronika;Tan, Jessica;Krammer, Florian
通讯作者：
Krammer, Florian
影响因子：
4.8
作者：
Lo, Megan;Kim, Hok Seon;Ernst, James A.
通讯作者：
Ernst, James A.