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Cross-Protective Abilities of Hyaluronic Acid Modified with Tetraglycine-l-octaarginine as a Mucosal Adjuvant against Infection with Heterologous Influenza Viruses.
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2019-11-18 , DOI: 10.1021/acs.bioconjchem.9b00644 Sohei Tanishita 1 , Masami Ukawa 1 , Takumi Tomono 1 , Yuki Yoshida 1 , Takumi Tsujioka 1 , Kohei Miyata 2 , Etsuo Tobita 2 , Tomofumi Uto 3 , Masanori Baba 4 , Shinji Sakuma 1
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2019-11-18 , DOI: 10.1021/acs.bioconjchem.9b00644 Sohei Tanishita 1 , Masami Ukawa 1 , Takumi Tomono 1 , Yuki Yoshida 1 , Takumi Tsujioka 1 , Kohei Miyata 2 , Etsuo Tobita 2 , Tomofumi Uto 3 , Masanori Baba 4 , Shinji Sakuma 1
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Mucosal vaccination, which secretion of immunoglobulin A (IgA) on the mucosa is accompanied by induction of immunoglobulin G (IgG) in the blood, is one of the most effective ways to circumvent influenza epidemics caused by incorrect prediction of epidemic viral strains or viral mutation. Secreted IgA is expected to prevent hosts from being infected with heterologous viruses because this antibody cross-reacts to strains other than those used for immunization. Our previous mouse experiments revealed that intranasal IgA with cross-reactivity was induced through nasal inoculation with inactivated whole viral particles of the H1N1 A/New Caledonia/20/99 IVR116 (NCL) strain in the presence of hyaluronic acid modified with tetraglycine-l-octaarginine. In the present study, heterologous influenza virus challenge was performed to validate a potential of the hyaluronic acid derivative as a mucosal adjuvant with cross-protective abilities. Serious weight loss was observed when mice were nasally inoculated with inactivated NCL viruses alone and subsequently exposed to mouse-adapted infectious viruses of the H1N1 A/Puerto Rico/8/34 (PR8) strain. The symptom associated with virus infection was hardly ever observed for mice inoculated with a mixture of the viral antigens and tetraglycine-l-octaarginine-linked hyaluronic acid, presumably due to high induction of IgG and IgA capable of cross-reacting to PR8 viruses. Less proliferation of PR8 viruses in those mice was also supported by an insignificant elevation of antibody levels through virus exposure. Our polysaccharide derivative enabled hosts to acquire adaptive immunity with cross-protective abilities against heterologous virus infection.
中文翻译：
四甘氨酸-l-辛精氨酸修饰的透明质酸作为粘膜佐剂对抗异源流感病毒感染的交叉保护能力。
粘膜疫苗接种使粘膜分泌免疫球蛋白A（IgA），同时诱导血液中免疫球蛋白G（IgG），是规避因错误预测流行病毒株或病毒突变而引起的流感流行的最有效方法之一。分泌的 IgA 有望防止宿主感染异源病毒，因为这种抗体与用于免疫的病毒株以外的病毒株发生交叉反应。我们之前的小鼠实验表明，在四甘氨酸-l-修饰的透明质酸存在下，通过鼻部接种 H1N1 A/新喀里多尼亚/20/99 IVR116 (NCL) 株的灭活完整病毒颗粒，诱导鼻内 IgA 具有交叉反应性。八精氨酸。在本研究中，进行异源流感病毒攻击以验证透明质酸衍生物作为具有交叉保护能力的粘膜佐剂的潜力。当小鼠仅经鼻接种灭活的 NCL 病毒并随后暴露于 H1N1 A/Puerto Rico/8/34 (PR8) 株的小鼠适应性感染病毒时，观察到严重的体重减轻。对于接种病毒抗原和四甘氨酸-1-辛精氨酸连接的透明质酸的混合物的小鼠来说，几乎没有观察到与病毒感染相关的症状，这可能是由于能够与PR8病毒交叉反应的IgG和IgA的高度诱导。这些小鼠体内 PR8 病毒的增殖较少，这也得到了病毒暴露后抗体水平轻微升高的支持。我们的多糖衍生物使宿主获得适应性免疫，具有针对异源病毒感染的交叉保护能力。
更新日期：2019-11-19
中文翻译：
四甘氨酸-l-辛精氨酸修饰的透明质酸作为粘膜佐剂对抗异源流感病毒感染的交叉保护能力。
粘膜疫苗接种使粘膜分泌免疫球蛋白A（IgA），同时诱导血液中免疫球蛋白G（IgG），是规避因错误预测流行病毒株或病毒突变而引起的流感流行的最有效方法之一。分泌的 IgA 有望防止宿主感染异源病毒，因为这种抗体与用于免疫的病毒株以外的病毒株发生交叉反应。我们之前的小鼠实验表明，在四甘氨酸-l-修饰的透明质酸存在下，通过鼻部接种 H1N1 A/新喀里多尼亚/20/99 IVR116 (NCL) 株的灭活完整病毒颗粒，诱导鼻内 IgA 具有交叉反应性。八精氨酸。在本研究中，进行异源流感病毒攻击以验证透明质酸衍生物作为具有交叉保护能力的粘膜佐剂的潜力。当小鼠仅经鼻接种灭活的 NCL 病毒并随后暴露于 H1N1 A/Puerto Rico/8/34 (PR8) 株的小鼠适应性感染病毒时，观察到严重的体重减轻。对于接种病毒抗原和四甘氨酸-1-辛精氨酸连接的透明质酸的混合物的小鼠来说，几乎没有观察到与病毒感染相关的症状，这可能是由于能够与PR8病毒交叉反应的IgG和IgA的高度诱导。这些小鼠体内 PR8 病毒的增殖较少，这也得到了病毒暴露后抗体水平轻微升高的支持。我们的多糖衍生物使宿主获得适应性免疫，具有针对异源病毒感染的交叉保护能力。
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