Viromimetic STING Agonist‐Loaded Hollow Polymeric Nanoparticles for Safe and Effective Vaccination against Middle East Respiratory Syndrome Coronavirus
Identifieur interne : 000329 ( Main/Exploration ); précédent : 000328; suivant : 000330Viromimetic STING Agonist‐Loaded Hollow Polymeric Nanoparticles for Safe and Effective Vaccination against Middle East Respiratory Syndrome Coronavirus
Auteurs : Leon Chien-Wei Lin ; Chen-Yu Huang ; Bing-Yu Yao ; Jung-Chen Lin ; Anurodh Agrawal ; Abdullah Algaissi ; Bi-Hung Peng ; Yu-Han Liu ; Ping-Han Huang ; Rong-Huay Juang ; Yuan-Chih Chang ; Chien-Te Tseng ; Hui-Wen Chen ; Che-Ming Jack HuSource :
- Advanced Functional Materials [ 1616-301X ] ; 2019.
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‐CoV‐permissive 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.
Url:
DOI: 10.1002/adfm.201807616
PubMed: NONE
PubMed Central: 7161765
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en"><title>Abstract</title>
<p>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‐CoV‐permissive 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.</p>
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<name sortKey="Hu, Che Ing Jack" sort="Hu, Che Ing Jack" uniqKey="Hu C" first="Che-Ming Jack" last="Hu">Che-Ming Jack Hu</name>
<name sortKey="Huang, Chen U" sort="Huang, Chen U" uniqKey="Huang C" first="Chen-Yu" last="Huang">Chen-Yu Huang</name>
<name sortKey="Huang, Ping An" sort="Huang, Ping An" uniqKey="Huang P" first="Ping-Han" last="Huang">Ping-Han Huang</name>
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<name sortKey="Lin, Jung Hen" sort="Lin, Jung Hen" uniqKey="Lin J" first="Jung-Chen" last="Lin">Jung-Chen Lin</name>
<name sortKey="Lin, Leon Chien Ei" sort="Lin, Leon Chien Ei" uniqKey="Lin L" first="Leon Chien-Wei" last="Lin">Leon Chien-Wei Lin</name>
<name sortKey="Liu, Yu An" sort="Liu, Yu An" uniqKey="Liu Y" first="Yu-Han" last="Liu">Yu-Han Liu</name>
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<name sortKey="Tseng, Chien E" sort="Tseng, Chien E" uniqKey="Tseng C" first="Chien-Te" last="Tseng">Chien-Te Tseng</name>
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