Grandi Alberto, Tomasi Michele, Ullah Irfan, Bertelli Cinzia, Vanzo Teresa, Accordini Silvia, Gagliardi Assunta, Zanella Ilaria, Benedet Mattia, Corbellari Riccardo, Di Lascio Gabriele, Tamburini Silvia, Caproni Elena, Croia Lorenzo, Ravà Micol, Fumagalli Valeria, Di Lucia Pietro, Marotta Davide, Sala Eleonora, Iannacone Matteo, Kumar Priti, Mothes Walther, Uchil Pradeep D, Cherepanov Peter, Bolognesi Martino, Pizzato Massimo, Grandi Guido
Toscana Life Sciences Foundation, Via Fiorentina 1, 53100 Siena, Italy.
BiOMViS Srl, Via Fiorentina 1, 53100 Siena, Italy.
Vaccines (Basel). 2023 Sep 29;11(10):1546. doi: 10.3390/vaccines11101546.
The vaccination campaign against SARS-CoV-2 relies on the world-wide availability of effective vaccines, with a potential need of 20 billion vaccine doses to fully vaccinate the world population. To reach this goal, the manufacturing and logistic processes should be affordable to all countries, irrespective of economical and climatic conditions. Outer membrane vesicles (OMVs) are bacterial-derived vesicles that can be engineered to incorporate heterologous antigens. Given the inherent adjuvanticity, such modified OMVs can be used as vaccines to induce potent immune responses against the associated proteins. Here, we show that OMVs engineered to incorporate peptides derived from the receptor binding motif (RBM) of the spike protein from SARS-CoV-2 elicit an effective immune response in vaccinated mice, resulting in the production of neutralizing antibodies (nAbs) with a titre higher than 1:300. The immunity induced by the vaccine is sufficient to protect the animals from intranasal challenge with SARS-CoV-2, preventing both virus replication in the lungs and the pathology associated with virus infection. Furthermore, we show that OMVs can be effectively decorated with the RBM of the Omicron BA.1 variant and that such engineered OMVs induce nAbs against Omicron BA.1 and BA.5, as measured using the pseudovirus neutralization infectivity assay. Importantly, we show that the RBM ancestral-OMVs elicited antibodies which efficiently neutralize in vitro both the homologous ancestral strain, the Omicron BA.1 and BA.5 variants with a neutralization titre ranging from 1:100 to 1:1500, suggesting its potential use as a vaccine targeting diverse SARS-CoV-2 variants. Altogether, given the convenience associated with the ease of engineering, production and distribution, our results demonstrate that OMV-based SARS-CoV-2 vaccines can be a crucial addition to the vaccines currently available.
针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的疫苗接种运动依赖于全球范围内有效疫苗的可及性，全面接种全球人口可能需要200亿剂疫苗。为实现这一目标，制造和物流过程应让所有国家都负担得起，无论其经济和气候条件如何。外膜囊泡（OMV）是细菌衍生的囊泡，可以进行工程改造以掺入异源抗原。鉴于其固有的佐剂性，这种经过修饰的OMV可以用作疫苗，以诱导针对相关蛋白质的强效免疫反应。在这里，我们表明，经过工程改造以掺入源自SARS-CoV-2刺突蛋白受体结合基序（RBM）的肽的OMV，在接种疫苗的小鼠中引发了有效的免疫反应，产生了滴度高于1:300的中和抗体（nAbs）。疫苗诱导的免疫力足以保护动物免受SARS-CoV-2鼻内攻击，防止病毒在肺部复制以及与病毒感染相关的病理变化。此外，我们表明，OMV可以用奥密克戎BA.1变体的RBM有效修饰，并且使用假病毒中和感染性测定法测量，这种经过工程改造的OMV可诱导针对奥密克戎BA.1和BA.5的nAbs。重要的是，我们表明，RBM祖先型OMV引发的抗体在体外能有效中和同源祖先毒株、奥密克戎BA.1和BA.5变体，中和滴度范围为1:100至1:1500，这表明其有可能用作针对多种SARS-CoV-2变体的疫苗。总之，鉴于工程改造、生产和分发的便利性，我们的结果表明，基于OMV的SARS-CoV-2疫苗可以成为现有疫苗的重要补充。
