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猪的免疫原性和安全性研究 PHH-1V,一种 SARS-CoV-2 RBD 融合异二聚体疫苗候选物。

Immunogenicity and safety in pigs of PHH-1V, a SARS-CoV-2 RBD fusion heterodimer vaccine candidate.

机构信息

HIPRA, Avda. La Selva, 135, 17170 Amer (Girona), Spain.

HIPRA, Avda. La Selva, 135, 17170 Amer (Girona), Spain.

出版信息

Vaccine. 2023 Aug 7;41(35):5072-5078. doi: 10.1016/j.vaccine.2023.07.008. Epub 2023 Jul 16.

DOI:10.1016/j.vaccine.2023.07.008
PMID:37460353
Abstract

The continuing high global incidence of COVID-19 and the undervaccinated status of billions of persons strongly motivate the development of a new generation of efficacious vaccines. We have developed an adjuvanted vaccine candidate, PHH-1V, based on a protein comprising the receptor binding domain (RBD) of the Beta variant of SARS-CoV-2 fused in tandem with the equivalent domain of the Alpha variant, with its immunogenicity, safety and efficacy previously demonstrated in mouse models. In the present study, we immunized pigs with different doses of PHH-1V in a prime-and-boost scheme showing PHH-1V to exhibit an excellent safety profile in pigs and to produce a solid RBD-specific humoral response with neutralising antibodies to 7 distinct SARS-CoV-2 variants of concern, with the induction of a significant IFNγ T-cell response. We conclude that PHH-1V is safe and elicits a robust immune response to SARS-CoV-2 in pigs, a large animal preclinical model.

摘要

持续高的全球 COVID-19 发病率和数十亿人的未接种疫苗状态强烈促使开发新一代有效的疫苗。我们已经开发了一种基于蛋白的佐剂疫苗候选物 PHH-1V,该蛋白由 SARS-CoV-2 的 Beta 变体的受体结合域(RBD)与 Alpha 变体的等效结构域串联融合而成,其免疫原性、安全性和功效已在小鼠模型中得到证实。在本研究中,我们采用不同剂量的 PHH-1V 对猪进行了初免-加强免疫,结果表明 PHH-1V 在猪中具有优异的安全性,并产生了针对 7 种不同关切的 SARS-CoV-2 变体的 RBD 特异性体液反应和中和抗体,同时诱导了显著的 IFNγ T 细胞反应。我们得出结论,PHH-1V 是安全的,并在大动物临床前模型猪中引发了针对 SARS-CoV-2 的强烈免疫反应。

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