A therapeutic hepatitis B mRNA vaccine with strong immunogenicity and persistent virological suppression

Zhao, Huajun; Yu, Yating; Liu, Zhenguang; Huang, Lulu; Yang, Ailu; Jiao, Lina; Song, Zuchen; Wang, Yucan; Bao, Cuiping; Yu, Ruijin; Lin, Yan; Wang, Guan; Wang, De‐Yi; Han, Qiuju; Zhang, Liang; Huang, Liang; Zhang, Jian; Yang, Yong; Lin, Ang

doi:10.1101/2022.11.18.517095

Cited by 3 publications

(5 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…VZV mRNA vaccine (ZOSAL) was prepared as previously described [ 22 , 23 ]. In brief, mRNA encoding for VZV gE immunogen was synthesized in vitro by T7 polymerase-mediated transcription from a linearized DNA template.…”

Section: Mrna Vaccine Preparationmentioning

confidence: 99%

“…In the current study, we developed a novel VZV mRNA vaccine (named as ZOSAL) containing sequence-optimized mRNAs encoding full-length glycoprotein E (gE) encapsulated in an ionizable lipid nanoparticle (LNP) formulation using our well-established platforms [ 22–24 ]. The immunogenicity of ZOSAL was thoroughly evaluated and compared side-by-side with the benchmark vaccine (Shingrix) in adult mice, aged mice, and importantly in rhesus macaques.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Herpes zoster mRNA vaccine induces superior vaccine immunity over licensed vaccine in mice and rhesus macaques

Huang,

Zhao,

Zhao

et al. 2024

Emerging Microbes & Infections

Self Cite

View full text Add to dashboard Cite

Herpes zoster remains an important global health issue and mainly occurs in aged and immunocompromised individuals with an early exposure history to Varicella Zoster Virus (VZV). Although the licensed vaccine Shingrix has remarkably high efficacy, undesired reactogenicity and increasing global demand causing vaccine shortage urged the development of improved or novel VZV vaccines. In this study, we developed a novel VZV mRNA vaccine candidate (named as ZOSAL) containing sequence-optimized mRNAs encoding full-length glycoprotein E encapsulated in an ionizable lipid nanoparticle. In mice and rhesus macaques, ZOSAL demonstrated superior immunogenicity and safety in multiple aspects over Shingrix, especially in the induction of strong T-cell immunity. Transcriptomic analysis revealed that both ZOSAL and Shingrix could robustly activate innate immune compartments, especially Type-I IFN signalling and antigen processing/presentation. Multivariate correlation analysis further identified several early factors of innate compartments that can predict the magnitude of T-cell responses, which further increased our understanding of the mode of action of two different VZV vaccine modalities. Collectively, our data demonstrated the superiority of VZV mRNA vaccine over licensed subunit vaccine. The mRNA platform therefore holds prospects for further investigations in next-generation VZV vaccine development.

show abstract

Section: Mrna Vaccine Preparationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Herpes zoster mRNA vaccine induces superior vaccine immunity over licensed vaccine in mice and rhesus macaques

Huang,

Zhao,

Zhao

et al. 2024

Emerging Microbes & Infections

Self Cite

View full text Add to dashboard Cite

show abstract

“…VZV mRNA vaccine (ZOSAL) was prepared as previously described [17,18]. In brief, mRNA encoding for VZV gE immunogen was synthesized in vitro by T7 polymerase-mediated transcription from a linearized DNA template.…”

Section: Mrna Vaccine Preparationmentioning

confidence: 99%

“…In the current study, we developed a novel VZV mRNA vaccine (named as ZOSAL) containing sequence-optimized mRNAs encoding full-length glycoprotein E (gE) encapsulated in an ionizable lipid nanoparticle (LNP) formulation using our well-established platforms [17][18][19]. The immunogenicity of ZOSAL was thoroughly evaluated and compared side-by-side with the benchmark vaccine (Shingrix) in adult mice, aged mice, and importantly in rhesus macaques.…”

Section: Introductionmentioning

confidence: 99%

Herpes zoster mRNA vaccine induces superior vaccine immunity over licensed vaccine in mice and rhesus macaques

Huang,

Zhao,

Zhao

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Herpes zoster remains an important global health issue and mainly occurs in aged and immunocompromised individuals with an early exposure history to Varicella Zoster Virus (VZV). Although the licensed vaccine Shingrix has a remarkably high efficacy, undesired reactogenicity and increasing global demand causing vaccine shortage urged the development of improved or novel VZV vaccines. In this study, we developed a novel VZV mRNA vaccine candidate (named as ZOSAL) containing sequence-optimized mRNAs encoding full-length glycoprotein E encapsulated in an ionizable lipid nanoparticle. In mice and rhesus macaques, ZOSAL demonstrated superior immunogenicity and safety in multiple aspects over Shingrix, especially in the induction of strong T cell immunity. Transcriptomic analysis revealed that both ZOSAL and Shingrix could robustly activate innate immune compartments, especially Type-I IFN signaling and antigen processing/presentation. Multivariate correlation analysis further identified several early factors of innate compartments that can predict the magnitude of T cell responses, which further increased our understanding of the mode of action of two different VZV vaccine modalities. Collectively, our data demonstrated the superiority of VZV mRNA vaccine over licensed subunit vaccine. The mRNA platform therefore holds prospects for further investigations in next-generation VZV vaccine development.

show abstract

“…Efforts to develop novel vaccines include the use of RNA-and viral vector-based approaches. RNA lipid nanoparticle (LNP) formulations and adenovirus (AdV)-based vaccines have performed well in pre-clinical studies [9][10][11]. Recombinant adeno-associated viral vectors (rAAVs) have also been explored for vaccine development.…”

Section: Introductionmentioning

confidence: 99%

AAV Immunotoxicity: Implications in Anti-HBV Gene Therapy

Jacobs,

Dogbey,

Mnyandu

et al. 2023

Microorganisms

View full text Add to dashboard Cite

Hepatitis B virus (HBV) has afflicted humankind for decades and there is still no treatment that can clear the infection. The development of recombinant adeno-associated virus (rAAV)-based gene therapy for HBV infection has become important in recent years and research has made exciting leaps. Initial studies, mainly using mouse models, showed that rAAVs are non-toxic and induce minimal immune responses. However, several later studies demonstrated rAAV toxicity, which is inextricably associated with immunogenicity. This is a major setback for the progression of rAAV-based therapies toward clinical application. Research aimed at understanding the mechanisms behind rAAV immunity and toxicity has contributed significantly to the inception of approaches to overcoming these challenges. The target tissue, the features of the vector, and the vector dose are some of the determinants of AAV toxicity, with the latter being associated with the most severe adverse events. This review discusses our current understanding of rAAV immunogenicity, toxicity, and approaches to overcoming these hurdles. How this information and current knowledge about HBV biology and immunity can be harnessed in the efforts to design safe and effective anti-HBV rAAVs is discussed.

show abstract

A therapeutic hepatitis B mRNA vaccine with strong immunogenicity and persistent virological suppression

Cited by 3 publications

References 46 publications

Herpes zoster mRNA vaccine induces superior vaccine immunity over licensed vaccine in mice and rhesus macaques

Herpes zoster mRNA vaccine induces superior vaccine immunity over licensed vaccine in mice and rhesus macaques

Herpes zoster mRNA vaccine induces superior vaccine immunity over licensed vaccine in mice and rhesus macaques

AAV Immunotoxicity: Implications in Anti-HBV Gene Therapy

Contact Info

Product

Resources

About