Generation of potent cellular and humoral immunity against SARS-CoV-2 antigens via conjugation to a polymeric glyco-adjuvant

Abstract

The SARS-CoV-2 virus has caused an unprecedented global crisis, and curtailing its spread requires an effective vaccine which elicits a diverse and robust immune response. We have previously shown that vaccines made of a polymeric glyco-adjuvant conjugated to an antigen were effective in triggering such a response in other disease models and hypothesized that the technology could be adapted to create an effective vaccine against SARS-CoV-2. The core of the vaccine platform is the copolymer p(Man-TLR7), composed of monomers with pendant mannose or a toll-like receptor 7 (TLR7) agonist. Thus, p(Man-TLR7) is designed to target relevant antigen-presenting cells (APCs) via mannose-binding receptors and then activate TLR7 upon endocytosis. The p(Man-TLR7) construct is amenable to conjugation to protein antigens such as the Spike protein of SARS-CoV-2, yielding Spike-p(Man-TLR7). Here, we demonstrate Spike-p(Man-TLR7) vaccination elicits robust antigen-specific cellular and humoral responses in mice. In adult and elderly wild-type mice, vaccination with Spike-p(Man-TLR7) generates high and long-lasting titers of anti-Spike IgGs, with neutralizing titers exceeding levels in convalescent human serum. Interestingly, adsorbing Spike-p(Man-TLR7) to the depot-forming adjuvant alum amplified the broadly neutralizing humoral responses to levels matching those in mice vaccinated with formulations based off of clinically-approved adjuvants. Additionally, we observed an increase in germinal center B cells, antigen-specific antibody secreting cells, activated T follicular helper cells, and polyfunctional Th1-cytokine producing CD4 + and CD8 + T cells. We conclude that Spike-p(Man-TLR7) is an attractive, next-generation subunit vaccine candidate, capable of inducing durable and robust antibody and T cell responses.

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

“…The purine-rich RNA is a natural ligand for TLR7, which induces the innate immune response to the invading pathogen (22)(23)(24)(25). Due to the important role of TLR7 in activating the immune system, many studies focused on the conjugation of TLR7 agonists to antigens for enhancing immune responses (26)(27)(28)(29).…”

Biocompatible Films of Calcium Alginate Inactivate Enveloped Viruses Such as SARS-CoV-2

“…The COVID-19 pandemic has forced material engineers to develop and search for alternative materials capable of inactivating SARS-CoV-2 [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. In this regard, sodium alginate (SA) has shown antiviral activity against several types of viruses [ 9 ] and has been seen to possess excellent chemical, physical, and biological properties that render this biopolymer very useful for an immense range of industrial applications [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”

A Perspective on the Roles of Adjuvants in Developing Highly Potent COVID-19 Vaccines

“…Jeffrey and colleagues developed another S protein-based vaccine platform called Man-TLR7. They found that this polymeric glycol-adjuvant improved the immunogenicity of the S protein by inducing a powerful neutralizing humoral immune response and highquality cellular immune responses [56]. Pamela's team invented an intranasal vaccine candidate, which formulated S protein with a nanoemulsion (NE) that activated NLRP3 and TLRs with the RNA agonist RIG-I (IVT DI).…”