Abstract
BackgroundThe ongoing COVID-19 pandemic has resulted in 185 million recorded cases and over 4 million deaths worldwide. Several COVID-19 vaccines have been approved for emergency use in humans and are being used in many countries. However, all the approved vaccines are administered by intramuscular injection and this may not prevent upper airway infection or viral transmission.ResultsHere, we describe a novel, intranasally delivered COVID-19 vaccine based on a helper-dependent adenoviral (HD-Ad) vector. The vaccine (HD-Ad_RBD) produces a soluble secreted form of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and we show it induced robust mucosal and systemic immunity. Moreover, intranasal immunization of K18-hACE2 mice with HD-Ad_RBD using a prime-boost regimen, resulted in complete protection of the upper respiratory tract against SARS-CoV-2 infection.ConclusionOur approaches provide a powerful platform for constructing highly effective vaccines targeting SARS-CoV-2 and its emerging variants.
Highlights
The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) [1], has resulted in more than 180 million confirmed cases and at least 4 million deaths worldwide
SARS-CoV-2 is a global health priority and a number of vaccine platforms have already been tested [2]. These include inactivated virus [3, 4], naked DNA delivered by electroporation [5], mRNA delivered by lipid nanoparticles [6,7,8,9], viral vectors such as nonreplicating adenovirus [10,11,12,13,14,15,16,17], replication-competent vesicular stomatitis virus (VSV) [18] or yellow fever virus [19], and recombinant protein delivered by nanoparticles [20, 21]
To examine the expression and secretion of the receptor binding domain (RBD), epithelial cells (A549 and IB3) were transfected with HD-Ad_RBD at different dosages and the cell lysates and culture supernatants were analyzed by Western blot
Summary
The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) [1], has resulted in more than 180 million confirmed cases and at least 4 million deaths worldwide. Unlike the vectors used in the currently approved Adbased SARS-CoV-2 vaccines [24,25,26], helper-dependent adenoviral vectors (HD-Ad) are third generation vectors completely devoid of adenoviral coding sequences [27] They were designed to eliminate the expression of unwanted adenoviral proteins [28, 29] and they have been used primarily in preclinical tests of in vivo gene delivery for the treatment of inherited genetic diseases [28, 30]. HD-Ad has a high cloning capacity (up to 36 kb) for transgenes, making it possible to deliver large genes or multiple genes in one vector These features, in conjunction with its excellent safety profile, make HD-Ad an attractive platform for the development of a SARS-CoV-2 vaccine. All the approved vaccines are administered by intramuscular injection and this may not prevent upper airway infection or viral transmission
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