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

• Published in: Biomaterials 2021-11, Vol.278, p.121159-121159, Article 121159
• Main Authors: Gray, Laura T., Raczy, Michal M., Briquez, Priscilla S., Marchell, Tiffany M., Alpar, Aaron T., Wallace, Rachel P., Volpatti, Lisa R., Sasso, Maria Stella, Cao, Shijie, Nguyen, Mindy, Mansurov, Aslan, Budina, Erica, Watkins, Elyse A., Solanki, Ani, Mitrousis, Nikolaos, Reda, Joseph W., Yu, Shann S., Tremain, Andrew C., Wang, Ruyi, Nicolaescu, Vlad, Furlong, Kevin, Dvorkin, Steve, Manicassamy, Balaji, Randall, Glenn, Wilson, D. Scott, Kwissa, Marcin, Swartz, Melody A., Hubbell, Jeffrey A.
• Format: Article
• Language: English
• Subjects: Adjuvant; Adjuvants, Immunologic; Aged; Animals; Antibodies, Neutralizing; Antibodies, Viral; CD8-Positive T-Lymphocytes; COVID-19; COVID-19 vaccine; COVID-19 Vaccines; Glycopolymers; Humans; Immunity, Cellular; Immunity, Humoral; Mice; Polymer-protein conjugates; Polymeric glyco-adjuvant; SARS-CoV-2; Subunit vaccine formulation
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2021.121159

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.