Intranasal Multiepitope PD‐L1‐siRNA‐Based Nanovaccine: The Next‐Gen COVID‐19 Immunotherapy

Intranasal Multiepitope PD‐L1‐siRNA‐Based Nanovaccine: The Next‐Gen COVID‐19 Immunotherapy

Abstract The first approved vaccines for human use against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) are nanotechnology‐based. Although they are modular, rapidly produced, and can reduce disease severity, the currently available vaccines are restricted in preventing infection, str...

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Main Authors: Rita C. Acúrcio, Ron Kleiner, Daniella Vaskovich‐Koubi, Bárbara Carreira, Yulia Liubomirski, Carolina Palma, Adva Yeheskel, Eilam Yeini, Ana S. Viana, Vera Ferreira, Carlos Araújo, Michael Mor, Natalia T. Freund, Eran Bacharach, João Gonçalves, Mira Toister‐Achituv, Manon Fabregue, Solene Matthieu, Capucine Guerry, Ana Zarubica, Sarit Aviel‐Ronen, Helena F. Florindo, Ronit Satchi‐Fainaro
Format: Article
Language:English
Published: Wiley 2024-10-01
Series:Advanced Science
Subjects:
Dendritic cells
Intranasal
MHC class I and MHC class II peptides
Nanovaccines
PD‐1/PD‐L1 immune checkpoints
SARS‐CoV‐2
Online Access:https://doi.org/10.1002/advs.202404159
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Summary:Abstract The first approved vaccines for human use against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) are nanotechnology‐based. Although they are modular, rapidly produced, and can reduce disease severity, the currently available vaccines are restricted in preventing infection, stressing the global demand for novel preventive vaccine technologies. Bearing this in mind, we set out to develop a flexible nanovaccine platform for nasal administration to induce mucosal immunity, which is fundamental for optimal protection against respiratory virus infection. The next‐generation multiepitope nanovaccines co‐deliver immunogenic peptides, selected by an immunoinformatic workflow, along with adjuvants and regulators of the PD‐L1 expression. As a case study, we focused on SARS‐CoV‐2 peptides as relevant antigens to validate the approach. This platform can evoke both local and systemic cellular‐ and humoral‐specific responses against SARS‐CoV‐2. This led to the secretion of immunoglobulin A (IgA), capable of neutralizing SARS‐CoV‐2, including variants of concern, following a heterologous immunization strategy. Considering the limitations of the required cold chain distribution for current nanotechnology‐based vaccines, it is shown that the lyophilized nanovaccine is stable for long‐term at room temperature and retains its in vivo efficacy upon reconstitution. This makes it particularly relevant for developing countries and offers a modular system adaptable to future viral threats.
ISSN:2198-3844

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