Journal article
Generation of potent cellular and humoral immunity against SARS-CoV-2 antigens via conjugation to a polymeric glyco-adjuvant
Biomaterials, Vol.278, 121159
11/2021
DOI: 10.1016/j.biomaterials.2021.121159
PMCID: PMC8482845
PMID: 34634664
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.
Details
- Title: Subtitle
- Generation of potent cellular and humoral immunity against SARS-CoV-2 antigens via conjugation to a polymeric glyco-adjuvant
- Creators
- Laura T. Gray - University of ChicagoMichal M. Raczy - University of ChicagoPriscilla S. Briquez - University of ChicagoTiffany M. Marchell - University of ChicagoAaron T. Alpar - University of ChicagoRachel P. Wallace - University of ChicagoLisa R. Volpatti - University of ChicagoMaria Stella Sasso - University of ChicagoShijie Cao - University of ChicagoMindy Nguyen - University of ChicagoAslan Mansurov - University of ChicagoErica Budina - University of ChicagoElyse A. Watkins - University of ChicagoAni Solanki - University of ChicagoNikolaos Mitrousis - University of ChicagoJoseph W. Reda - University of ChicagoShann S. Yu - University of ChicagoAndrew C. Tremain - University of ChicagoRuyi Wang - University of ChicagoVlad Nicolaescu - University of ChicagoKevin Furlong - University of ChicagoSteve Dvorkin - University of ChicagoBalaji Manicassamy - University of IowaGlenn Randall - University of ChicagoD. Scott Wilson - University of ChicagoMarcin Kwissa - University of ChicagoMelody A. Swartz - University of ChicagoJeffrey A. Hubbell - University of Chicago
- Resource Type
- Journal article
- Publication Details
- Biomaterials, Vol.278, 121159
- DOI
- 10.1016/j.biomaterials.2021.121159
- PMID
- 34634664
- PMCID
- PMC8482845
- NLM abbreviation
- Biomaterials
- ISSN
- 0142-9612
- eISSN
- 1878-5905
- Publisher
- Elsevier Ltd
- Language
- English
- Date published
- 11/2021
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984297322302771
Metrics
18 Record Views