Single-dose intranasal vaccination elicits systemic and mucosal immunity against SARS-CoV-2

Abstract

Despite remarkable progress in the development and authorization of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a need to validate vaccine platforms for broader application. The current intramuscular vaccines are designed to elicit systemic immunity without conferring mucosal immunity in the nasal compartment, which is the first barrier that SARS-CoV-2 virus breaches before dissemination to the lung. We report the development of an intranasal subunit vaccine that uses lyophilized spike protein and liposomal STING agonist as an adjuvant. This vaccine induces systemic neutralizing antibodies, IgA in the lung and nasal compartments, and T-cell responses in the lung of mice. Single-cell RNA sequencing confirmed the coordinated activation of T/B-cell responses in a germinal center-like manner within the nasal-associated lymphoid tissues, confirming its role as an inductive site to enable durable immunity. The ability to elicit immunity in the respiratory tract can prevent the establishment of infection in individuals and prevent disease transmission.Mucosal vaccination can stimulate both systemic and mucosal immunity and has the advantage of being a non-invasive procedure suitable for immunization of large populations. However, mucosal vaccination is

A protein vaccine with Alum/c-GAMP/poly(I:C) rapidly boosts robust immunity against SARS-CoV-2 and variants of concern

“…7,8 However, the relatively simple structure and weak immunogenicity of recombinant S1 protein limit the development of S1-based SARS-CoV-2 vaccines. Additional adjuvants are necessary to initiate a robust protective response quickly, such as Alum, 9,10 invariant natural killer T (iNKT) cell agonist, 11 stimulator of interferon genes (STING) agonist, 12,13 and Toll-like receptor (TLR) agonists including imidazoquinoline, 14 CpG, 15,16 Pam 3 CSK 4 17 and MPLA. 16,18,19 In the development of SARS-CoV-2 protein vaccines, a single adjuvant is often insufficient to induce potent and optimal immune responses to fulfill different immunological needs.…”

Nanoagent-based theranostic strategies against human coronaviruses

“…Delta variant, one of the most contagious SARS-CoV-2 strains, has attracted great attention recently due to its remarkable global transmission and strong immune escape ability in patients [115]. It has 8-fold less sensitivity to vaccine-elicited antibodies than the wild-type SARS-CoV-2 (D614G strain) [116]. Benefitting from the feasible abilities to load or conjugate mutable antigens on nanoagents, nanovaccines have excellent advantages for prolonged antigen presentation and enhanced immunogenicity against the Delta variant.…”

Strategies for fighting pandemic virus infections: Integration of virology and drug delivery

“…We also encapsulated CDNs into a LNP composed of YSK12-C4, an ionizable lipid, and the treatment with the LNP caused elevated levels of serum type I IFN and induced an antitumor effect against lung metastasis [ 193 ]. Although there are few verifications of drugs for the treatment of pandemic respiratory virus infections, the use on these drugs in conjunction with a lipid-based nano-DDS as a vaccine adjuvant against seasonal influenza and COVID-19 has been reported [ 233 , 234 ].…”

“…Nasal co-administration of the liposome and whole inactivated H1N1 vaccine induced the production of mucosal IgA and memory CD8 + cells, and showed strong cross-protection against H3N2 and H5N1. In addition to the influenza vaccine, a liposomal STING ligand was employed for a COVID-19 vaccine [ 234 ]. The composition of the liposome was quite similar [ 233 ] and the liposome had a negative charge and a PEG lipid.…”

“…The composition of the liposome was quite similar [ 233 ] and the liposome had a negative charge and a PEG lipid. A single-dose nasal vaccination of the liposomal STING ligand elicited strong systemic and mucosal immune responses against SARS-CoV-2 [ 234 ]. Taken together, even with PRR ligands, strong mucosal immunity can be induced when appropriate lipid-based nano-DDS is used, and it can be inferred that ligands recognized by intracellular PRRs may be suitable as an adjuvant for mucosal vaccines against the pandemic respiratory virus.…”