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AF03 佐剂增强了经许可的季节性四价流感疫苗在小鼠体内诱导的抗血凝素和抗神经氨酸酶免疫应答。

AF03 adjuvant improves anti-hemagglutinin and anti-neuraminidase immune responses induced by licensed seasonal quadrivalent influenza vaccines in mice.

机构信息

Sanofi, Cambridge, MA, USA.

Sanofi, Cambridge, MA, USA.

出版信息

Vaccine. 2023 Mar 17;41(12):2022-2034. doi: 10.1016/j.vaccine.2023.02.034. Epub 2023 Feb 18.

Abstract

Seasonal influenza remains a serious public health concern as the viral infection spreads easily from person to person and due to antigenic drift of neutralizing epitopes. Vaccination is the best method for disease prevention, however current seasonal influenza vaccines stimulate antibodies which are often effective against only antigenically similar strains. To boost the immune responses and increase vaccine effectiveness, adjuvants have been used for the past 20 years. The current study explores the use of oil-in-water adjuvant, AF03 to improve an immunogenicity of 2 licensed vaccines. A standard-dose inactivated quadrivalent influenza vaccine (IIV4-SD), containing both hemagglutinin (HA) and neuraminidase (NA) antigens, and recombinant quadrivalent influenza vaccine (RIV4), containing only HA-antigen were adjuvanted with AF03 in naïve BALB/c mouse model. Functional HA-specific antibody titers against all four homologous vaccine strains were enhanced by AF03, indicating potential increase in protective immunity. An increase in HA-specific total immunoglobulin G (IgG) binding titers were detected against homologous HAs, heterologous panel of 30 H3 HAs and seven Influenza B HAs. The neuraminidase inhibition (NAI) activity was significantly higher in IIV4-SD-AF03 group. Use of AF03 adjuvant improved the immune response to two influenza vaccines in a mouse model via an increase in functional and total antibodies against NA and a broad panel of HA-antigens.

摘要

季节性流感仍然是一个严重的公共卫生问题,因为这种病毒很容易在人与人之间传播,而且中和表位的抗原性漂移。疫苗接种是预防疾病的最佳方法,然而,目前的季节性流感疫苗刺激的抗体通常仅对抗原相似的菌株有效。为了增强免疫反应并提高疫苗的有效性,过去 20 年来一直使用佐剂。本研究探讨了使用油包水佐剂 AF03 来提高两种许可疫苗的免疫原性。在 naive BALB/c 小鼠模型中,用 AF03 对标准剂量的灭活四价流感疫苗(IIV4-SD)和仅含血凝素(HA)抗原的重组四价流感疫苗(RIV4)进行佐剂处理。AF03 增强了针对所有四种同源疫苗株的功能性 HA 特异性抗体滴度,表明潜在的保护免疫力增加。针对同源 HAs、30 种 H3 HAs 和 7 种流感 B HAs 的异源面板,检测到 HA 特异性总免疫球蛋白 G(IgG)结合滴度增加。在 IIV4-SD-AF03 组中,神经氨酸酶抑制(NAI)活性显著升高。AF03 佐剂的使用通过增加针对 NA 和广泛的 HA 抗原的功能性和总抗体,改善了两种流感疫苗在小鼠模型中的免疫反应。

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