PMID- 36655751
OWN - NLM
STAT- MEDLINE
DCOM- 20230228
LR  - 20240202
IS  - 1096-9071 (Electronic)
IS  - 0146-6615 (Print)
IS  - 0146-6615 (Linking)
VI  - 95
IP  - 2
DP  - 2023 Feb
TI  - A hepatitis B virus core antigen-based virus-like particle vaccine expressing 
      SARS-CoV-2 B and T cell epitopes induces epitope-specific humoral and 
      cell-mediated immune responses but confers limited protection against SARS-CoV-2 
      infection.
PG  - e28503
LID - 10.1002/jmv.28503 [doi]
AB  - The hepatitis B virus core antigen (HBcAg) tolerates insertion of foreign 
      epitopes and maintains its ability to self-assemble into virus-like particles 
      (VLPs). We constructed a ∆HBcAg-based VLP vaccine expressing three predicted 
      severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B and T cell 
      epitopes and determined its immunogenicity and protective efficacy. The 
      recombinant ∆HBcAg-SARS-CoV-2 protein was expressed in Escherichia coli, 
      purified, and shown to form VLPs. K18-hACE2 transgenic C57BL/6 mice were 
      immunized intramuscularly with ∆HBcAg VLP control (n = 15) or ∆HBcAg-SARS-CoV-2 
      VLP vaccine (n = 15). One week after the 2nd booster and before virus challenge, 
      five ∆HBcAg-SARS-CoV-2 vaccinated mice were euthanized to evaluate 
      epitope-specific immune responses. There is a statistically significant increase 
      in epitope-specific Immunoglobulin G (IgG) response, and statistically higher 
      interleukin 6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) expression 
      levels in ∆HBcAg-SARS-CoV-2 VLP-vaccinated mice compared to ∆HBcAg VLP controls. 
      While not statistically significant, the ∆HBcAg-SARS-CoV-2 VLP mice had 
      numerically more memory CD8+ T-cells, and 3/5 mice also had numerically higher 
      levels of interferon gamma (IFN-gamma) and tumor necrosis factor (TNF). After 
      challenge with SARS-CoV-2, ∆HBcAg-SARS-CoV-2 immunized mice had numerically lower 
      viral RNA loads in the lung, and slightly higher survival, but the differences 
      are not statistically significant. These results indicate that the 
      ∆HBcAg-SARS-CoV-2 VLP vaccine elicits epitope-specific humoral and cell-mediated 
      immune responses but they were insufficient against SARS-CoV-2 infection.
CI  - (c) 2023 Wiley Periodicals LLC.
FAU - Hassebroek, Anna M
AU  - Hassebroek AM
AD  - Department of Biomedical Sciences and Pathobiology, Center for Emerging, 
      Zoonotic, and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State 
      University, Blacksburg, Virginia, USA.
FAU - Sooryanarain, Harini
AU  - Sooryanarain H
AD  - Department of Biomedical Sciences and Pathobiology, Center for Emerging, 
      Zoonotic, and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State 
      University, Blacksburg, Virginia, USA.
FAU - Heffron, Connie L
AU  - Heffron CL
AD  - Department of Biomedical Sciences and Pathobiology, Center for Emerging, 
      Zoonotic, and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State 
      University, Blacksburg, Virginia, USA.
FAU - Hawks, Seth A
AU  - Hawks SA
AD  - Department of Biomedical Sciences and Pathobiology, Center for Emerging, 
      Zoonotic, and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State 
      University, Blacksburg, Virginia, USA.
FAU - LeRoith, Tanya
AU  - LeRoith T
AUID- ORCID: 0000-0002-1196-6949
AD  - Department of Biomedical Sciences and Pathobiology, Center for Emerging, 
      Zoonotic, and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State 
      University, Blacksburg, Virginia, USA.
FAU - Cecere, Thomas E
AU  - Cecere TE
AD  - Department of Biomedical Sciences and Pathobiology, Center for Emerging, 
      Zoonotic, and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State 
      University, Blacksburg, Virginia, USA.
FAU - Stone, William B
AU  - Stone WB
AD  - Department of Entomology, Center for Emerging, Zoonotic, and Arthropod-borne 
      Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, 
      Virginia, USA.
FAU - Walter, Debra
AU  - Walter D
AD  - Department of Biological System Engineering, Center for Emerging, Zoonotic, and 
      Arthropod-borne Pathogens, Virginia Polytechnic Institute and State University, 
      Blacksburg, Virginia, USA.
FAU - Mahsoub, Hassan M
AU  - Mahsoub HM
AD  - Department of Biomedical Sciences and Pathobiology, Center for Emerging, 
      Zoonotic, and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State 
      University, Blacksburg, Virginia, USA.
FAU - Wang, Bo
AU  - Wang B
AUID- ORCID: 0000-0002-8560-9071
AD  - Department of Biomedical Sciences and Pathobiology, Center for Emerging, 
      Zoonotic, and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State 
      University, Blacksburg, Virginia, USA.
FAU - Tian, Debin
AU  - Tian D
AD  - Department of Biomedical Sciences and Pathobiology, Center for Emerging, 
      Zoonotic, and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State 
      University, Blacksburg, Virginia, USA.
FAU - Ivester, Hannah M
AU  - Ivester HM
AD  - Department of Biomedical Sciences and Pathobiology, Center for Emerging, 
      Zoonotic, and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State 
      University, Blacksburg, Virginia, USA.
FAU - Allen, Irving C
AU  - Allen IC
AD  - Department of Biomedical Sciences and Pathobiology, Center for Emerging, 
      Zoonotic, and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State 
      University, Blacksburg, Virginia, USA.
FAU - Auguste, Albert J
AU  - Auguste AJ
AD  - Department of Entomology, Center for Emerging, Zoonotic, and Arthropod-borne 
      Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, 
      Virginia, USA.
FAU - Duggal, Nisha K
AU  - Duggal NK
AD  - Department of Biomedical Sciences and Pathobiology, Center for Emerging, 
      Zoonotic, and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State 
      University, Blacksburg, Virginia, USA.
FAU - Zhang, Chenming
AU  - Zhang C
AD  - Department of Biological System Engineering, Center for Emerging, Zoonotic, and 
      Arthropod-borne Pathogens, Virginia Polytechnic Institute and State University, 
      Blacksburg, Virginia, USA.
FAU - Meng, Xiang-Jin
AU  - Meng XJ
AUID- ORCID: 0000-0002-2739-1334
AD  - Department of Biomedical Sciences and Pathobiology, Center for Emerging, 
      Zoonotic, and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State 
      University, Blacksburg, Virginia, USA.
LA  - eng
GR  - R01 AI153433/AI/NIAID NIH HHS/United States
GR  - NH/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Med Virol
JT  - Journal of medical virology
JID - 7705876
RN  - 0 (Hepatitis B Core Antigens)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Vaccines, Virus-Like Particle)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Hepatitis B Core Antigens/genetics
MH  - Hepatitis B virus/genetics
MH  - Epitopes, T-Lymphocyte
MH  - SARS-CoV-2
MH  - *Vaccines, Virus-Like Particle
MH  - *COVID-19
MH  - Mice, Inbred C57BL
MH  - Immunity, Cellular
MH  - Recombinant Proteins
PMC - PMC9974889
MID - NIHMS1867493
OTO - NOTNLM
OT  - B cell epitope
OT  - SARS-CoV-2
OT  - T cell epitope
OT  - cell-mediated immune response
OT  - hepatitis B core antigen (HBcAg)
OT  - humoral immune response
OT  - vaccine
OT  - virus-like particle (VLP)
COIS- Conflict of Interest The authors declare that they have no known competing 
      financial interests or personal relationships that influenced the work reported 
      herein.
EDAT- 2023/01/20 06:00
MHDA- 2023/03/03 06:00
PMCR- 2024/02/01
CRDT- 2023/01/19 06:53
PHST- 2023/01/11 00:00 [revised]
PHST- 2022/12/10 00:00 [received]
PHST- 2023/01/13 00:00 [accepted]
PHST- 2023/01/20 06:00 [pubmed]
PHST- 2023/03/03 06:00 [medline]
PHST- 2023/01/19 06:53 [entrez]
PHST- 2024/02/01 00:00 [pmc-release]
AID - 10.1002/jmv.28503 [doi]
PST - ppublish
SO  - J Med Virol. 2023 Feb;95(2):e28503. doi: 10.1002/jmv.28503.