National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
Henan Bioengineering Research Center, Zhengzhou 4500466, Henan, China.
Biomed Environ Sci. 2019 Jul;32(7):531-540. doi: 10.3967/bes2019.070.
To evaluate the effect of intranasal immunization with CTA1-DD as mucosal adjuvant combined with H3N2 split vaccine.
Mice were immunized intranasally with PBS (negative control), or H3N2 split vaccine (3 μg/mouse) alone, or CTA1-DD (5 μg/mouse) alone, or H3N2 split vaccine (3 μg/mouse) plus CTA1-DD (5 μg/mouse). Positive control mice were immunized intramuscularly with H3N2 split vaccine (3 μg/mouse) and alum adjuvant. All the mice were immunized twice, two weeks apart. Then sera and mucosal lavages were collected. The specific HI titers, IgM, IgG, IgA, and IgG subtypes were examined by ELISA. IFN-γ and IL-4 were test by ELISpot. In addition, two weeks after the last immunization, surivival after H3N2 virus lethal challenge was measured.
H3N2 split vaccine formulated with CTA1-DD could elicit higher IgM, IgG and hemagglutination inhibition titers in sera. Furthermore, using CTA1-DD as adjuvant significantly improved mucosal secretory IgA titers in bronchoalveolar lavages and vaginal lavages. Meanwhile this mucosal adjuvant could enhance Th-1-type responses and induce protective hemagglutination inhibition titers. Notably, the addition of CTA1-DD to split vaccine provided 100% protection against lethal infection by the H3N2 virus.
CTA1-DD could promote mucosal, humoral and cell-mediated immune responses, which supports the further development of CTA1-DD as a mucosal adjuvant for mucosal vaccines.
评估鼻内免疫 CTA1-DD 作为黏膜佐剂与 H3N2 裂解疫苗联合的效果。
用 PBS（阴性对照）、单独的 H3N2 裂解疫苗（3μg/只）、单独的 CTA1-DD（5μg/只）或 H3N2 裂解疫苗（3μg/只）加 CTA1-DD（5μg/只）经鼻内免疫小鼠。阳性对照小鼠经肌肉内免疫 H3N2 裂解疫苗（3μg/只）和铝佐剂。所有小鼠均间隔两周免疫两次。然后收集血清和黏膜冲洗液。通过 ELISA 检测特异性 HI 滴度、IgM、IgG、IgA 和 IgG 亚型。通过 ELISpot 检测 IFN-γ和 IL-4。此外，末次免疫后两周，测量 H3N2 病毒致死性攻击后的存活情况。
用 CTA1-DD 配制的 H3N2 裂解疫苗可在血清中引起更高的 IgM、IgG 和血凝抑制滴度。此外，使用 CTA1-DD 作为佐剂可显著提高支气管肺泡灌洗液和阴道冲洗液中的黏膜分泌型 IgA 滴度。同时，这种黏膜佐剂可增强 Th1 型反应，并诱导保护性血凝抑制滴度。值得注意的是，在裂解疫苗中添加 CTA1-DD 可提供对 H3N2 病毒致死性感染的 100%保护。
CTA1-DD 可促进黏膜、体液和细胞介导的免疫反应，支持 CTA1-DD 作为黏膜疫苗黏膜佐剂的进一步开发。
