Mucosal SARS-CoV-2 Nanoparticle Vaccine Based on Mucosal Adjuvants and Its Immune Effectiveness by Intranasal Administration

Abstract

SARS-CoV-2 is a respiratory virus that causes significant threats to human health. Mucosal immunity provides a first-line defense to prevent the infection of SARS-CoV-2 in the respiratory tract. Because most SARS-CoV-2 vaccines could not stimulate mucosal immunity in the respiratory tract, appropriate mucosal adjuvants or delivery systems are needed for mucosal vaccine development. Mannan, polyarginine, and 2′,3′-cGAMP are three mucosal adjuvants that could stimulate mucosal immunity. In the present study, the three adjuvants were assembled with a receptor-binding domain (RBD) by electrostatic interaction to generate a nanoparticle vaccine (RBD-MP-cG). RBD-MP-cG elicited mucosal IgA and IgG response in bronchoalveolar lavage and nasal lavage by intranasal administration. It induced a robust RBD-specific antibody response, high levels of protective neutralizing antibody, and ACE2-blocking activity in the mouse sera. It stimulated the splenic secretion of high levels of Th1-, Th2-, and Th17-type cytokines. Thus, RBD-MP-cG elicited strong mucosal immunity and systematic immunity by intranasal administration. RBD-MP-cG was expected to act as a safe, effective, and easily produced mucosal nanoparticle vaccine to combat the infection of SARS-CoV-2.

Emerging Cationic Nanovaccines

“…In a further effort to enhance the effectiveness of intranasal SARS-CoV-2 vaccines, the receptorbinding domain (RBD) of the SARS-CoV-2 spike protein was chemically conjugated to mannan; RBDmannan conjugate was then assembled to polyarginine and 2',3'-cGAMP, a potent stimulator of the STING pathway, through electrostatic interactions; this process resulted in slightly cationic NPs approximately 74 nm in diameter; NPs demonstrated high mRNA encapsulation efficiency and excellent biocompatibility; intranasal administration in mice elicited robust local immune responses, with high levels of mucosal IgA and IgG in nasal and bronchoalveolar lavage fluids, and strong systemic immune responses, including elevated levels of RBD-specific neutralizing antibodies; the formulation also promoted a balanced Th1/Th2/Th17 cytokine response, crucial for effective immune protection [169].…”

Self-Assembling Sulfated Lactobacillus Exopolysaccharide Nanoparticles as Adjuvants for SARS-CoV-2 Subunit Vaccine Elicit Potent Humoral and Cellular Immune Responses

“…Therefore, safe and effective vaccine adjuvants are required to enhance the immune effects of subunit vaccines including stable release of antigens and activation of innate and cellular immunity. With the increasing research on nanomaterials, nanoparticles (NPs) have been widely developed and applied as vaccine adjuvants. − NPs have unique physical and chemical properties and can consequently be used as a type of vaccine carrier to improve the efficacy and safety of vaccines and protect antigens from degradation and rapid release. , Furthermore, NPs can enhance the recognition and uptake of antigens by antigen-presenting cells and improve the immunogenicity and protective effect of vaccines by activating immune response. , Thus, NPs have been used in the development of vaccines for coronavirus, influenza, tuberculosis, and malaria, showing considerable potential as novel vaccine adjuvants. − …”

Extraordinary Titer and Broad Anti-SARS-CoV-2 Neutralization Induced by Stabilized RBD Nanoparticles from Strain BA.5

“…Among the approaches to increase breadth and potency, vaccines based on self-assembling nanoparticles appear to be especially promising [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. Such nanoparticle vaccines have multiple advantages.…”