Broad and Durable Humoral Responses Following Single Hydrogel Immunization of SARS‐CoV‐2 Subunit Vaccine

Abstract

Most vaccines require several immunizations to induce robust immunity, and indeed, most SARS‐CoV‐2 vaccines require an initial two‐shot regimen followed by several boosters to maintain efficacy. Such a complex series of immunizations unfortunately increases the cost and complexity of populations‐scale vaccination and reduces overall compliance and vaccination rate. In a rapidly evolving pandemic affected by the spread of immune‐escaping variants, there is an urgent need to develop vaccines capable of providing robust and durable immunity. In this work, a single immunization SARS‐CoV‐2 subunit vaccine is developed that can rapidly generate potent, broad, and durable humoral immunity. Injectable polymer–nanoparticle (PNP) hydrogels are leveraged as a depot technology for the sustained delivery of a nanoparticle antigen (RND‐NP) displaying multiple copies of the SARS‐CoV‐2 receptor‐binding domain (RBD) and potent adjuvants including CpG and 3M‐052. Compared to a clinically relevant prime‐boost regimen with soluble vaccines formulated with CpG/alum or 3M‐052/alum adjuvants, PNP hydrogel vaccines more rapidly generated higher, broader, and more durable antibody responses. Additionally, these single‐immunization hydrogel‐based vaccines elicit potent and consistent neutralizing responses. Overall, it is shown that PNP hydrogels elicit improved anti‐COVID immune responses with only a single administration, demonstrating their potential as critical technologies to enhance overall pandemic readiness.

Sustained Vaccine Exposure Elicits More Rapid, Consistent, and Broad Humoral Immune Responses to Multivalent Influenza Vaccines

“…In this work we have sought to fabricate an adjuvanted hydrogel platform that can be easily used in conjunction with commercial multivalent subunit or inactivated virus vaccines to enhance the potency, durability, and breadth of humoral immune responses. Our immunogenicity data indicate that sustained vaccine exposure with our PNP hydrogel technology ensures full seroconversion against all included viral strains, a development from our previous work which had only shown improvements in humoral immune responses with single antigen vaccines [52–54, 56–58] . The superior humoral immunity also extends to heterologous strains of influenza, where mice receiving hydrogel-based vaccines exhibited complete responses and comparable titers to those elicited by clinically relevant adjuvant technologies against the homologous strains.…”

Nanoparticle-Conjugated Toll-Like Receptor 9 Agonists Improve the Potency, Durability, and Breadth of COVID-19 Vaccines

“…These soluble vaccine groups received a prime immunization at week 0 and a boost immunization on week 3, with sera collected weekly from weeks 0–10 (Figure A). As we have previously demonstrated robust humoral responses with a single immunization of SARS-CoV-2 RBD hydrogel vaccines, , we also evaluated a single subcutaneous immunization of PNP hydrogels comprising spike antigen (20 μg) adjuvanted with either soluble CpG or CpG-NP (containing an equivalent of 40 μg of CpG) on week 0 (referred as CpG gel and CpG-NP gel, respectively). As with the prime-boost soluble vaccines, sera were collected weekly at weeks 0–10.…”

Biomaterial engineering strategies for B cell immunity modulations

“…187,188 A similar improvement was also achieved when delivering a self-assembled multivalent RBD-functional nanoparticle (RBD-NP) antigen using a PNP hydrogel. 174 These findings underscore the effectiveness and versatility of PNP hydrogel-mediated sustained vaccine delivery in generating robust, enduring, and broad antibody responses.…”