Enhanced Potency and Persistence of Immunity to Varicella-Zoster Virus Glycoprotein E in Mice by Addition of a Novel BC02 Compound Adjuvant
Herpes zoster (HZ) is one of two distinct syndromes caused by Varicella-zoster virus (VZV). A primary infection with VZV causes varicella in susceptible young children. After resolution of the primary infection, VZV establishes a lifelong latency within the cranial or dorsal root ganglia. With incre...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/10/4/529 |
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| author | Junli Li Lili Fu Yang Yang Guozhi Wang Aihua Zhao |
| author_facet | Junli Li Lili Fu Yang Yang Guozhi Wang Aihua Zhao |
| author_sort | Junli Li |
| collection | DOAJ |
| description | Herpes zoster (HZ) is one of two distinct syndromes caused by Varicella-zoster virus (VZV). A primary infection with VZV causes varicella in susceptible young children. After resolution of the primary infection, VZV establishes a lifelong latency within the cranial or dorsal root ganglia. With increasing age, family history of shingles, immunosuppression or other risk factors, there is a decline in the virus-specific T-cell-mediated immune (CMI) response which allows reactivation of latent VZV in the root ganglia resulting in HZ. There are currently two vaccines that have been approved to prevent HZ and postherpetic neuralgia (PHN) but one is a live attenuated vaccine, the protective effect of which is considered to decrease significantly with the age of the recipient. However, a recombinant subunit vaccine may provide targeted VZV-specific cellular and humoral immunity, giving it a more potent and longer-lasting protective effect against HZ. The current study reports the development of a novel adjuvant, BC02 (BCG CpG DNA compound adjuvants system 02), composed of Al(OH)<sub>3</sub> inorganic salt adjuvant and BC01 (BCG CpG DNA compound adjuvants system 01), a Toll-like receptor 9 (TLR9) agonist. Immunogenicity and compatibility with recombinant VZV glycoprotein E (gE) in mice were studied. The BC02-adjuvanted gE experimental vaccine was highly effective in eliciting both humoral and cellular immune responses to the recombinant gE glycoprotein and VZV-Oka in a mouse model. The efficient production and long-term persistence of gE and VZV-Oka-specific IFN-γ, IL-2-specific T cells and memory B cells in the early (1W), middle (7W), middle-late (15W), and final (27W) immune stages were established. Results of fluorescent antibody to membrane antigen (FAMA) and serum antibody plaque reduction tests also showed that the BC02 adjuvanted-gE experimental vaccine induced mice to secrete neutralizing antibodies against clinically isolated VZV strains. In combination, the current data suggest that the BC02 compound adjuvant offers a strategy to induce an appropriately strong cellular and humoral immunity against the VZV gE protein subunit to improve vaccine efficacy. |
| first_indexed | 2024-03-09T10:27:56Z |
| format | Article |
| id | doaj.art-31102f1fb1ff4cf69452e6b107634b37 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T10:27:56Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-31102f1fb1ff4cf69452e6b107634b372023-12-01T21:30:24ZengMDPI AGVaccines2076-393X2022-03-0110452910.3390/vaccines10040529Enhanced Potency and Persistence of Immunity to Varicella-Zoster Virus Glycoprotein E in Mice by Addition of a Novel BC02 Compound AdjuvantJunli Li0Lili Fu1Yang Yang2Guozhi Wang3Aihua Zhao4Division of Tuberculosis Vaccine and Allergen Products, Institute of Biological Product Control, National Institutes for Food and Drug Control, Beijing 102629, ChinaDivision of Tuberculosis Vaccine and Allergen Products, Institute of Biological Product Control, National Institutes for Food and Drug Control, Beijing 102629, ChinaDivision of Tuberculosis Vaccine and Allergen Products, Institute of Biological Product Control, National Institutes for Food and Drug Control, Beijing 102629, ChinaDivision of Tuberculosis Vaccine and Allergen Products, Institute of Biological Product Control, National Institutes for Food and Drug Control, Beijing 102629, ChinaDivision of Tuberculosis Vaccine and Allergen Products, Institute of Biological Product Control, National Institutes for Food and Drug Control, Beijing 102629, ChinaHerpes zoster (HZ) is one of two distinct syndromes caused by Varicella-zoster virus (VZV). A primary infection with VZV causes varicella in susceptible young children. After resolution of the primary infection, VZV establishes a lifelong latency within the cranial or dorsal root ganglia. With increasing age, family history of shingles, immunosuppression or other risk factors, there is a decline in the virus-specific T-cell-mediated immune (CMI) response which allows reactivation of latent VZV in the root ganglia resulting in HZ. There are currently two vaccines that have been approved to prevent HZ and postherpetic neuralgia (PHN) but one is a live attenuated vaccine, the protective effect of which is considered to decrease significantly with the age of the recipient. However, a recombinant subunit vaccine may provide targeted VZV-specific cellular and humoral immunity, giving it a more potent and longer-lasting protective effect against HZ. The current study reports the development of a novel adjuvant, BC02 (BCG CpG DNA compound adjuvants system 02), composed of Al(OH)<sub>3</sub> inorganic salt adjuvant and BC01 (BCG CpG DNA compound adjuvants system 01), a Toll-like receptor 9 (TLR9) agonist. Immunogenicity and compatibility with recombinant VZV glycoprotein E (gE) in mice were studied. The BC02-adjuvanted gE experimental vaccine was highly effective in eliciting both humoral and cellular immune responses to the recombinant gE glycoprotein and VZV-Oka in a mouse model. The efficient production and long-term persistence of gE and VZV-Oka-specific IFN-γ, IL-2-specific T cells and memory B cells in the early (1W), middle (7W), middle-late (15W), and final (27W) immune stages were established. Results of fluorescent antibody to membrane antigen (FAMA) and serum antibody plaque reduction tests also showed that the BC02 adjuvanted-gE experimental vaccine induced mice to secrete neutralizing antibodies against clinically isolated VZV strains. In combination, the current data suggest that the BC02 compound adjuvant offers a strategy to induce an appropriately strong cellular and humoral immunity against the VZV gE protein subunit to improve vaccine efficacy.https://www.mdpi.com/2076-393X/10/4/529varicella-zoster virusglycoprotein EHerpes zoster vaccineBC02 compound adjuvant |
| spellingShingle | Junli Li Lili Fu Yang Yang Guozhi Wang Aihua Zhao Enhanced Potency and Persistence of Immunity to Varicella-Zoster Virus Glycoprotein E in Mice by Addition of a Novel BC02 Compound Adjuvant Vaccines varicella-zoster virus glycoprotein E Herpes zoster vaccine BC02 compound adjuvant |
| title | Enhanced Potency and Persistence of Immunity to Varicella-Zoster Virus Glycoprotein E in Mice by Addition of a Novel BC02 Compound Adjuvant |
| title_full | Enhanced Potency and Persistence of Immunity to Varicella-Zoster Virus Glycoprotein E in Mice by Addition of a Novel BC02 Compound Adjuvant |
| title_fullStr | Enhanced Potency and Persistence of Immunity to Varicella-Zoster Virus Glycoprotein E in Mice by Addition of a Novel BC02 Compound Adjuvant |
| title_full_unstemmed | Enhanced Potency and Persistence of Immunity to Varicella-Zoster Virus Glycoprotein E in Mice by Addition of a Novel BC02 Compound Adjuvant |
| title_short | Enhanced Potency and Persistence of Immunity to Varicella-Zoster Virus Glycoprotein E in Mice by Addition of a Novel BC02 Compound Adjuvant |
| title_sort | enhanced potency and persistence of immunity to varicella zoster virus glycoprotein e in mice by addition of a novel bc02 compound adjuvant |
| topic | varicella-zoster virus glycoprotein E Herpes zoster vaccine BC02 compound adjuvant |
| url | https://www.mdpi.com/2076-393X/10/4/529 |
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