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佐剂介导的对经过计算优化的血凝素和神经氨酸酶疫苗的抗体反应差异。

Adjuvant-Mediated Differences in Antibody Responses to Computationally Optimized Hemagglutinin and Neuraminidase Vaccines.

机构信息

Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.

Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.

出版信息

Viruses. 2023 Jan 25;15(2):347. doi: 10.3390/v15020347.

Abstract

Computationally optimized broadly reactive antigens (COBRAs) are a next-generation universal influenza vaccine candidate. However, how these COBRAs induce antibody responses when combined with different adjuvants has not previously been well-characterized. Therefore, we performed in vivo studies with an HA-based H1 COBRA, Y2, and an NA-based N1 COBRA, N1-I, to assess this effect for the H1N1 subtype. We tested the adjuvants AddaVax, AddaS03, CpG, and Alhydrogel. AddaS03 performed the best, eliciting high IgG titers and hemagglutination inhibition (HAI) activity for Y2 immunizations. Interestingly, serum antibody epitopes were relatively similar across adjuvant groups. Moreover, following N1-I immunization with these adjuvants, AddaS03 also elicited the highest IgG and neuraminidase inhibition (NAI) titers against the 2009 pandemic virus, A/California/07/2009 (A/CA/09). These results inform adjuvant selection efforts for H1 and N1 COBRA HA and NA antigens in a mouse model.

摘要

计算优化的广谱反应性抗原(COBRAs)是下一代通用流感疫苗候选物。然而,这些 COBRAs 与不同佐剂结合时如何诱导抗体反应,以前尚未得到很好的描述。因此,我们使用基于 HA 的 H1 COBRA、Y2 和基于 NA 的 N1 COBRA、N1-I 进行了体内研究,以评估其对 H1N1 亚型的作用。我们测试了佐剂 AddaVax、AddaS03、CpG 和 Alhydrogel。AddaS03 表现最好,在 Y2 免疫接种时引起高 IgG 滴度和血凝抑制(HAI)活性。有趣的是,血清抗体表位在不同佐剂组之间相对相似。此外,用这些佐剂对 N1-I 进行免疫接种后,AddaS03 也引起了针对 2009 年大流行病毒 A/California/07/2009(A/CA/09)的最高 IgG 和神经氨酸酶抑制(NAI)滴度。这些结果为在小鼠模型中 H1 和 N1 COBRA HA 和 NA 抗原的佐剂选择提供了信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8897/9960755/8f8d9252dca4/viruses-15-00347-g001.jpg

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