MPLA-Adjuvanted Liposomes Encapsulating S-Trimer or RBD or S1, but Not S-ECD, Elicit Robust Neutralization Against SARS-CoV-2 and Variants of Concern

Abstract

Safe and effective vaccines are the best method to defeat worldwide SARS-CoV-2 and its circulating variants. The SARS-CoV-2 S protein and its subunits are the most attractive targets for the development of protein-based vaccines. In this study, we evaluated three lipophilic adjuvants, monophosphoryl lipid A (MPLA), Toll-like receptor (TLR) 1/2 ligand Pam 3 CSK 4 , and α-galactosylceramide ( α -GalCer), in liposomal and nonliposomal vaccines. The immunological results showed that the MPLA-adjuvanted liposomal vaccine induced the strongest humoral and cellular immunity. Therefore, we further performed a systematic comparison of S-trimer, S-ECD, S1, and RBD as antigens in MPLA-adjuvanted liposomes and found that, although these four vaccines all induced robust specific antibody responses, only S-trimer, S1, and RBD liposomes, but not S-ECD, elicited potent neutralizing antibody responses. Moreover, RBD, S-trimer, and S1 liposomes effectively neutralized variants (B.1.1.7/alpha, B.1.351/beta, P.1/gamma, B.1.617.2/delta, and B.1.1.529/omicron). These results provide important information for the subunit vaccine design against SARS-CoV-2 and its variants.

Alum Adjuvant and Built-in TLR7 Agonist Synergistically Enhance Anti-MUC1 Immune Responses for Cancer Vaccine

“…Toll-like receptors (TLRs) are pattern-recognition receptors (PRRs) found in many immune cells such as macrophages and dendritic cells (DCs) (15)(16)(17)(18). TLRs can recognize nucleic acid molecules or cell wall components of pathogens to the innate immune system, and then regulate the activation of antigenpresenting cells (APCs) (19)(20)(21). The purine-rich RNA is a natural ligand for TLR7, which induces the innate immune response to the invading pathogen (22)(23)(24)(25).…”

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

“…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. An alternative strategy is to employ combined adjuvants with synergistic effects to improve vaccine efficacy.…”

Toll-Like Receptor Signaling in Severe Acute Respiratory Syndrome Coronavirus 2-Induced Innate Immune Responses and the Potential Application Value of Toll-Like Receptor Immunomodulators in Patients With Coronavirus Disease 2019

“…Recently, a biomaterial COVID-19 vaccine based on mesoporous silica rods (MSRs) and loaded with MPLA, granulocyte-macrophage colony-stimulating factor (GM-CSF), and SARS-CoV-2 viral protein antigens was shown to slowly release their cargo and form subcutaneous scaffolds that recruited and activated antigen-presenting cells (APCs) at the local site to generate adaptive immune responses ( Langellotto et al, 2021 ). The SARS-CoV-2 is still mutating; however, the MPLA-adjuvanted antigens like S-trimer/MPLA, RBD/MPLA, and S1/MPLA remain to induce a strong humoral and cellular immune responses against spike variants, including alpha, beta, gamma, delta, and omicron ( Wang et al, 2022 ). Another TLR4 agonist, inulin acetate (InAc), which is a plant-based polymer, has been reported to induce high IgG1, IgG2a, and sIgA titers against antigens in serum after intranasal immunization using antigen-loaded InAc nanoparticles (InAc-NPs); this approach resulted in a strong memory response indicative of both humoral and cellular immune activation, and may be useful in the development of a COVID-19 vaccine ( Bakkari et al, 2021 ).…”