Viromimetic STING Agonist‐Loaded Hollow Polymeric Nanoparticles for Safe and Effective Vaccination against Middle East Respiratory Syndrome Coronavirus

Abstract

The continued threat of emerging, highly lethal infectious pathogens such as Middle East respiratory syndrome coronavirus (MERS-CoV) calls for the development of novel vaccine technology that offers safe and effective prophylactic measures. Here, a novel nanoparticle vaccine is developed to deliver subunit viral antigens and STING agonists in a virus-like fashion. STING agonists are first encapsulated into capsid-like hollow polymeric nanoparticles, which show multiple favorable attributes, including a pH-responsive release profile, prominent local immune activation, and reduced systemic reactogenicity. Upon subsequent antigen conjugation, the nanoparticles carry morphological semblance to native virions and facilitate codelivery of antigens and STING agonists to draining lymph nodes and immune cells for immune potentiation. Nanoparticle vaccine effectiveness is supported by the elicitation of potent neutralization antibody and antigen-specific T cell responses in mice immunized with a MERS-CoV nanoparticle vaccine candidate. Using a MERS-CoVpermissive transgenic mouse model, it is shown that mice immunized with this nanoparticle-based MERS-CoV vaccine are protected against a lethal challenge of MERS-CoV without triggering undesirable eosinophilic immunopathology. Together, the biocompatible hollow nanoparticle described herein provides an excellent strategy for delivering both subunit vaccine candidates and novel adjuvants, enabling accelerated development of effective and safe vaccines against emerging viral pathogens.

Adjuvants for Coronavirus Vaccines

“…This adjuvant significantly activates innate immune response through activating TLR7 and enhancing the chemotaxis of professional antigen-presenting cells (APC) ( 71 ). Moreover, some novel adjuvants such as STING agonist, Advax, and AS01 B , which is an adjuvant formulated in recombinant zoster vaccine Shingrix, exhibit advantages for long-lasting immune responses ( 46 , 59 , 72 ). Advax, a delta inulin microparticle adjuvant, augmented the induction of neutralizing antibodies along with the existence of memory B cells and a robust, long-lasting T-cell IFN-γ response when it was formulated in recombinant or inactivated SARS-CoV vaccines ( 46 ).…”

<p>Induction of Robust Immune Responses by CpG-ODN-Loaded Hollow Polymeric Nanoparticles for Antiviral and Vaccine Applications in Chickens</p>

“…Using a water in oil in water (w/o/w) double emulsion technique, CpGencapsulating PLGA thin-shell nanoparticles (CpG-NP) were prepared as described previously. 18 Briefly, a polymer solution was prepared by dissolving 50 mg of PLGA (poly(dl-lactide-coglycolide, purchased from LACTEL Absorbable Polymers)) in dichloromethane. The inner aqueous phase was prepared by dissolving CpG in the phosphate buffer (pH 7).…”

“…Various forms of PLGA nanoparticles have been prepared to combat pressing human infections, including influenza, dengue, malaria, and Middle East respiratory syndrome coronavirus. 18,19 For applications in chickens, CpG-loaded PLGA particles have been applied in combination with inactivated influenza vaccine. 20 However, the large particle diameter (682.03 nm) for the particulate adjuvant in the study may have hammered its transport to the lymphoid tissues, 20 resulting marginal improvement in vaccine effectiveness.…”

“…Towards combatting avian infections, the present research adopts a recently developed PLGA-based hollow nanoparticle for CpG delivery. 18 The adjuvant uptake, dendritic cell activation, immunity-related gene expression, and antiviral ability were rigorously assessed and compared between free CpG and CpG-NP. Also, in vivo immunostimulating efficacy as a vaccine adjuvant was evaluated upon coupling with a subunit protein antigen.…”

Development of a copper-graphene nanocomposite based transparent coating with antiviral activity against influenza virus

“…CDC FLUVIEW] and different coronaviruses cause mild flu-like symptoms to severe respiratory infections (SARS (De Wit et al 2016) and MERS (Lin et al 2019) coronavirus epidemics during 2002 and 2012 respectively) (Fehr and Perlman 2015). Clearly, recurring respiratory infections caused by these viruses are becoming one of the global human health problem.…”