一种旨在诱导新冠病毒特异性CD8 T细胞的金纳米颗粒/肽疫苗：瑞士的一项双盲、随机、1期研究。

A gold nanoparticle/peptide vaccine designed to induce SARS-CoV-2-specific CD8 T cells: a double-blind, randomized, phase 1 study in Switzerland.

作者信息

Besson Juliette, Audran Régine, Karlen Maxime, Miauton Alix, Hajjami Hélène Maby-El, Warpelin-Decrausaz Loane, Sene Loredana, Schaufelberger Sylvain, Faivre Vincent, Faouzi Mohamed, Hartley Mary-Anne, Spertini François, Genton Blaise

机构信息

Tropical, Travel and Vaccination Clinic, Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.

Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Lausanne, Switzerland.

出版信息

BMC Infect Dis. 2025 Apr 7;25(1):472. doi: 10.1186/s12879-025-10844-3.

BACKGROUND

New vaccines with broader protection against SARS-CoV-2 are needed to reduce the risk of immune escape and provide broad and long-lasting cellular immunity. The objectives of the naNO-COVID trial were to evaluate the safety and immunogenicity of a CD8 + T cell, gold nanoparticle-based, peptide COVID-19 vaccine.

METHODS

A randomized, double-blind, vehicle-controlled, phase 1 trial in healthy adults to receive PepGNP-Covid19 or Vehicle-GNP, followed over 180 days, using a dose-escalation strategy.

RESULTS

Twenty participants received PepGNP-Covid19 (low dose [LD] or high dose [HD], n = 10 each) and six Vehicle-GNP (LD or HD, n = 3 each). Vaccinations were safe. No serious adverse events were reported. Most of the adverse events were mild, two adverse events of special interest related to the product (fever and fatigue). Reactogenicity was similar overall between vaccine, comparator, and doses. Virus-specific humoral responses in LD PepGNP-Covid19 and Vehicle-GNP groups coincided with SARS-CoV-2 infections. PepGNP-Covid19 vaccination induced the modulation of Covid19-specific CD137 + CD69 + CD8 + , and an increase at day 35 particularly in central and effector memory T cells in LD group, and in late effector memory cells in HD group.

CONCLUSIONS

The favourable safety profile and cellular responses observed support further development of PepGNP-Covid19.

TRIAL REGISTRATION

ClinicalTrials.gov, NCT05113862, approved 09.11.2021.

背景

需要研发出对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）具有更广泛保护作用的新型疫苗，以降低免疫逃逸风险，并提供广泛且持久的细胞免疫。naNO-COVID试验的目的是评估一种基于金纳米颗粒的CD8 + T细胞肽COVID-19疫苗的安全性和免疫原性。

方法

在健康成年人中进行一项随机、双盲、载体对照的1期试验，采用剂量递增策略，让受试者接受PepGNP-Covid19或载体-金纳米颗粒（Vehicle-GNP），并随访180天。

结果

20名参与者接受了PepGNP-Covid19（低剂量[LD]或高剂量[HD]，各n = 10），6名参与者接受了载体-金纳米颗粒（LD或HD，各n = 3）。疫苗接种是安全的。未报告严重不良事件。大多数不良事件为轻度，有两项与产品相关的特殊不良事件（发热和疲劳）。疫苗、对照剂和不同剂量之间的总体反应原性相似。LD PepGNP-Covid19组和载体-金纳米颗粒组中的病毒特异性体液反应与SARS-CoV-2感染一致。PepGNP-Covid19疫苗接种诱导了Covid19特异性CD137 + CD69 + CD8 + 的调节，在第35天时增加，特别是LD组的中央和效应记忆T细胞以及HD组的晚期效应记忆细胞。