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TitleSelf-assembling nanoparticle engineered from the ferritinophagy complex as a rabies virus vaccine candidate.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 8601, Year 2024
Publish dateOct 4, 2024
AuthorsDan Fu / Wenming Wang / Yan Zhang / Fan Zhang / Pinyi Yang / Chun Yang / Yufei Tian / Renqi Yao / Jingwu Jian / Zixian Sun / Nan Zhang / Zhiyu Ni / Zihe Rao / Lei Zhao / Yu Guo /
PubMed AbstractOver the past decade, there has been a growing interest in ferritin-based vaccines due to their enhanced antigen immunogenicity and favorable safety profiles, with several vaccine candidates ...Over the past decade, there has been a growing interest in ferritin-based vaccines due to their enhanced antigen immunogenicity and favorable safety profiles, with several vaccine candidates targeting various pathogens advancing to phase I clinical trials. Nevertheless, challenges associated with particle heterogeneity, improper assembly and unanticipated immunogenicity due to the bulky protein adaptor have impeded further advancement. To overcome these challenges, we devise a universal ferritin-adaptor delivery platform based on structural insights derived from the natural ferritinophagy complex of the human ferritin heavy chain (FTH1) and the nuclear receptor coactivator 4 (NCOA4). The engineered ferritinophagy (Fagy)-tag peptide demonstrate significantly enhanced binding affinity to the 24-mer ferritin nanoparticle, enabling efficient antigen presentation. Subsequently, we construct a self-assembling rabies virus (RABV) vaccine candidate by noncovalently conjugating the Fagy-tagged glycoprotein domain III (G) of RABV to the ferritin nanoparticle, maintaining superior homogeneity, stability and immunogenicity. This vaccine candidate induces potent, rapid, and durable immune responses, and protects female mice against the authentic RABV challenge after single-dose administration. Furthermore, this universal, ferritin-based antigen conjugating strategy offers significant potential for developing vaccine against diverse pathogens and diseases.
External linksNat Commun / PubMed:39366932 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.02 - 2.3 Å
Structure data

37566

8wiq

EMDB-37566, PDB-8wiq:
NCOA4/FTH1 complex
Method: EM (single particle) / Resolution: 2.19 Å

37578

8wjf

EMDB-37578, PDB-8wjf:
Peptide 10/FTH1 complex
Method: EM (single particle) / Resolution: 2.02 Å

PDB-8wie:
Peptide 10-1/FTH1-1 Complex
Method: X-RAY DIFFRACTION / Resolution: 2.3 Å

Chemicals

ChemComp-FE:
Unknown entry

ChemComp-CA:
Unknown entry

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
KeywordsMETAL BINDING PROTEIN / Nano-delivery platform / De novo Design / Ferritin / Rabies virus Glycoprotein domain III (RABV-GDIII) / GDIII-Ferritin Nano-vaccine / stabilized / Strong immune response

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