Subunit Nanovaccine with Potent Cellular and Mucosal Immunity for COVID-19

Abstract

To combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, we formulated the S1 subunit of the virus with two adjuvants, amphiphilic adjuvant monophosphoryl lipid A for Toll-like receptor 4 and CpG oligodeoxynucleotide for Toll-like receptor 9, into cationic liposomes to produce a potent, safer, and translatable nanovaccine. The nanovaccine can efficiently elicit a humoral immune response and strong IgA antibodies in mice. The sera from the vaccinated mice significantly inhibit SARS-CoV-2 from infecting Vero cells. Moreover, relative to the free S1 with a traditional Alum adjuvant, the nanovaccine can elicit strong T-cell immunity by activating both CD4 + and CD8 + cells.

State-of-the-Art of Nanodiagnostics and Nanotherapeutics against SARS-CoV-2

“… 154 Generally, the intramuscular administration route is preferred in vaccination; however, it would be more efficient to design vaccine delivery systems for targeting mucosal tissues or to be administered subcutaneously. 155 , 156 Furthermore, encapsulation of antigens inside NPs provides sustained-release properties that prevent adverse reactions in patients and ensure prolonged antigen presentation. 24 Cationic NPs could be used for entrapment or encapsulation of anionic DNA or RNA vaccines.…”

“… 177 Alum-formulated vaccines might show induction of Th2 responses. 156 On the contrary, vaccines that activated Th1 illustrated boosted immunities without lung immunopathology. 178 Th1 activation after immunization with the VLP plus alum vaccine could be attributed to the VLP properties.…”

“…In this respect, Liu et al recently developed cationic liposomes, surface electrostatically functionalized with a S1 subunit of SARS-CoV-2 ( Figure 8 ). 156 Further, two adjuvants including TLR-9 agonist (CpG oligodeoxynucleotide) and TLR-4 agonist (amphiphilic adjuvant monophosphoryl lipid A) molecules were loaded inside the particle core and lipid bilayer, respectively. The adjuvant molecules serve as PAMPs that could be recognized by TLRs to start the activation of T cell responses.…”

“… Scheme for a liposomal vaccine, surface-decorated with the S1 subunit of SARS-CoV-2 with TLR-4 and TLR-9 agonists entrapped in the phospholipid bilayer and the core of the liposome, respectively. Reprinted in part with permission from ref ( 156 ). Copyright 2020 American Chemical Society.…”

Nanomedicine: A Diagnostic and Therapeutic Approach to COVID-19

“…This NP based vaccine incorporates the RBD subunit of the spike protein combined with two adjuvants: Monophosphoryl Lipid A (MPLA) and CpG-ODN, which stimulate TLR4 and TLR9, respectively. The vaccination of mice was achieved in three stages (original shot and two boosters) and resulted in a potent and protective T cell response accompanied by neutralizing IgA antibodies (190). This nanovaccine is currently in clinical phase 3 testing and in light of the promising results, a large-scale manufacturing plant is under construction (191).…”