Hydrogel-Based Slow Release of a Receptor-Binding Domain Subunit Vaccine Elicits Neutralizing Antibody Responses Against SARS-CoV-2.

Emily C Gale,Abigail E Powell,Gillie A Roth,Eric A Appel,Peter S Kim,Ben S Ou,Abigail K Grosskopf,Bali Pulendran,Emily L Meany,Jerry Yan,Andrea I D'Aquino,Vittoria C T M Picece,Julia Adamska

doi:10.1002/adma.202104362

Emily C Gale, Abigail E Powell + Show 11 more

Open Access

https://doi.org/10.1002/adma.202104362

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Abstract

The development of effective vaccines that can be rapidly manufactured and distributed worldwide is necessary to mitigate the devastating health and economic impacts of pandemics like COVID‐19. The receptor‐binding domain (RBD) of the SARS‐CoV‐2 spike protein, which mediates host cell entry of the virus, is an appealing antigen for subunit vaccines because it is efficient to manufacture, highly stable, and a target for neutralizing antibodies. Unfortunately, RBD is poorly immunogenic. While most subunit vaccines are commonly formulated with adjuvants to enhance their immunogenicity, clinically‐relevant adjuvants Alum, AddaVax, and CpG/Alum are found unable to elicit neutralizing responses following a prime‐boost immunization. Here, it has been shown that sustained delivery of an RBD subunit vaccine comprising CpG/Alum adjuvant in an injectable polymer‐nanoparticle (PNP) hydrogel elicited potent anti‐RBD and anti‐spike antibody titers, providing broader protection against SARS‐CoV‐2 variants of concern compared to bolus administration of the same vaccine and vaccines comprising other clinically‐relevant adjuvant systems. Notably, a SARS‐CoV‐2 spike‐pseudotyped lentivirus neutralization assay revealed that hydrogel‐based vaccines elicited potent neutralizing responses when bolus vaccines did not. Together, these results suggest that slow delivery of RBD subunit vaccines with PNP hydrogels can significantly enhance the immunogenicity of RBD and induce neutralizing humoral immunity.

Highlights

The COVID-19 pandemic has had devastating health and economic impacts globally since SARS-CoV-2 first infected humans in late 2019
It has been shown that sustained delivery of an receptor-binding domain (RBD) subunit vaccine comprising CpG/Alum adjuvant in an injectable polymer-nanoparticle (PNP) hydrogel elicited potent anti-RBD and anti-spike antibody titers, providing broader protection against SARS-CoV-2 variants of concern compared to bolus administration of the same vaccine and vaccines comprising other clinically-relevant adjuvant systems
The PNP hydrogel platform is compatible with many physiochemically distinct molecules, which allowed us to screen a variety of adjuvant combinations before further pursuing CpG and Alum

Summary

Introduction

The COVID-19 pandemic has had devastating health and economic impacts globally since SARS-CoV-2 first infected humans in late 2019. COVID-19 has caused over 3.5 million deaths globally, including over 580 000 deaths in the US alone.[1] behavioral and contact tracing interventions have slowed the spread and vaccines are becoming available in some regions, case numbers remain high in many parts of the world. High rates of asymptomatic transmission and the lack of effective treatments have made the virus difficult to contain.[2] Deployment of effective vaccines is a critical global health priority toward ending the COVID-19 pandemic. COVID-19 has reinforced the importance of developing vaccine platforms that can be rapidly adapted to respond to future pandemics

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