RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
T Lymphocyte Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Cell. 2022 Dec 8;185(25):4811-4825.e17. doi: 10.1016/j.cell.2022.11.006. Epub 2022 Nov 10.
Pediatric SARS-CoV-2 vaccines are needed that elicit immunity directly in the airways as well as systemically. Building on pediatric parainfluenza virus vaccines in clinical development, we generated a live-attenuated parainfluenza-virus-vectored vaccine candidate expressing SARS-CoV-2 prefusion-stabilized spike (S) protein (B/HPIV3/S-6P) and evaluated its immunogenicity and protective efficacy in rhesus macaques. A single intranasal/intratracheal dose of B/HPIV3/S-6P induced strong S-specific airway mucosal immunoglobulin A (IgA) and IgG responses. High levels of S-specific antibodies were also induced in serum, which efficiently neutralized SARS-CoV-2 variants of concern of alpha, beta, and delta lineages, while their ability to neutralize Omicron sub-lineages was lower. Furthermore, B/HPIV3/S-6P induced robust systemic and pulmonary S-specific CD4 and CD8 T cell responses, including tissue-resident memory cells in the lungs. Following challenge, SARS-CoV-2 replication was undetectable in airways and lung tissues of immunized macaques. B/HPIV3/S-6P will be evaluated clinically as pediatric intranasal SARS-CoV-2/parainfluenza virus type 3 vaccine.
需要在呼吸道和全身都能引发免疫的儿科 SARS-CoV-2 疫苗。我们在正在临床开发的小儿副流感病毒疫苗的基础上,生成了一种表达 SARS-CoV-2 预融合稳定 Spike(S)蛋白的活减毒副流感病毒载体候选疫苗(B/HPIV3/S-6P),并在恒河猴中评估了其免疫原性和保护效力。单次鼻内/气管内剂量的 B/HPIV3/S-6P 可诱导强烈的 S 特异性气道黏膜免疫球蛋白 A(IgA)和 IgG 应答。还在血清中诱导了高水平的 S 特异性抗体,这些抗体能有效地中和α、β和δ谱系的 SARS-CoV-2 变体,而对奥密克戎亚谱系的中和能力较低。此外,B/HPIV3/S-6P 诱导了强烈的全身和肺部 S 特异性 CD4 和 CD8 T 细胞应答,包括肺部的组织驻留记忆细胞。在攻毒后,免疫猴的呼吸道和肺部组织中均无法检测到 SARS-CoV-2 复制。B/HPIV3/S-6P 将作为儿科鼻内 SARS-CoV-2/副流感病毒 3 疫苗进行临床评估。
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