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Chimeric rabies virus-like particles containing membrane-anchored GM-CSF enhances the immune response against rabies virus.

Kang H, Qi Y, Wang H, Zheng X, Gao Y, Li N, Yang S, Xia X - Viruses (2015)

Bottom Line: The EVLP-G was successfully produced in insect cells by coinfection with three recombinant baculoviruses expressing G, M, and GM-CSF, respectively.EVLP-G was found to induce a significantly increased RABV-specific virus-neutralizing antibody and elicit a larger and broader antibody subclass responses compared with the standard rabies VLP (sRVLP, consisting of G and M).The EVLP-G also elicited significantly more IFN-γ- or IL-4-secreting CD4+ and CD8+ T cells than the sRVLP.

View Article: PubMed Central - PubMed

Affiliation: College of Veterinary Medicine, South China Agricultural University, 483 Wushan Road, Guangzhou 510642, China. kang1989462@sina.com.

ABSTRACT
Rabies remains an important public health threat in most developing countries. To develop a more effective and safe vaccine against rabies, we have constructed a chimeric rabies virus-like particle (VLP), which containing glycoprotein (G) and matrix protein (M) of rabies virus (RABV) Evelyn-Rokitnicki-Abelseth (ERA) strain, and membrane-anchored granulocyte-macrophage colony-stimulating factor (GM-CSF), and it was named of EVLP-G. The immunogenicity and protective efficacy of EVLP-G against RABV were evaluated by intramuscular administration in a mouse model. The EVLP-G was successfully produced in insect cells by coinfection with three recombinant baculoviruses expressing G, M, and GM-CSF, respectively. The membrane-anchored GM-CSF possesses a strong adjuvant activity. More B cells and dendritic cells (DCs) were recruited and/or activated in inguinal lymph nodes in mice immunized with EVLP-G. EVLP-G was found to induce a significantly increased RABV-specific virus-neutralizing antibody and elicit a larger and broader antibody subclass responses compared with the standard rabies VLP (sRVLP, consisting of G and M). The EVLP-G also elicited significantly more IFN-γ- or IL-4-secreting CD4+ and CD8+ T cells than the sRVLP. Moreover, the immune responses induced by EVLP-G protect all vaccinated mice from lethal challenge with RABV. These results suggest that EVLP-G has the potential to be developed as a novel vaccine candidate for the prevention and control of animal rabies.

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Challenge test in mice. All mice from each group (n = 8) were challenged with 100 × IMLD50 of the RABV street stain at 4 weeks after the last vaccination by i.m. route, and the observed for 21 days. The survival of mice in each group at different times after challenge were recorded.
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viruses-07-01134-f007: Challenge test in mice. All mice from each group (n = 8) were challenged with 100 × IMLD50 of the RABV street stain at 4 weeks after the last vaccination by i.m. route, and the observed for 21 days. The survival of mice in each group at different times after challenge were recorded.

Mentions: To further evaluate whether the immune response induced by EVLP-G can protect against RABV, mice were challenged with 100 × IMLD50 RABV street strain (Figure 7). All mice mock immunized with PBS died of rabies within nine days of exposure to RABV challenge. In the EVLP-immunized group, two mice developed typical clinical symptoms of rabies and were humanely sacrificed at 12 days after infection, resulting in a 75% survival in that group. However, all mice from EVLP-G group were successfully protected against the high dose RABV challenge, and no clinical signs of rabies were observed in these mice during the 21-day observation period. RABV antigens were detected in the brains of mice that died from the challenge. The results of challenge experiment demonstrated that the immune responses induced by EVLP-G in mice can provide complete protection against a lethal challenge with high dose of RABV street strain.


Chimeric rabies virus-like particles containing membrane-anchored GM-CSF enhances the immune response against rabies virus.

Kang H, Qi Y, Wang H, Zheng X, Gao Y, Li N, Yang S, Xia X - Viruses (2015)

Challenge test in mice. All mice from each group (n = 8) were challenged with 100 × IMLD50 of the RABV street stain at 4 weeks after the last vaccination by i.m. route, and the observed for 21 days. The survival of mice in each group at different times after challenge were recorded.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4379564&req=5

viruses-07-01134-f007: Challenge test in mice. All mice from each group (n = 8) were challenged with 100 × IMLD50 of the RABV street stain at 4 weeks after the last vaccination by i.m. route, and the observed for 21 days. The survival of mice in each group at different times after challenge were recorded.
Mentions: To further evaluate whether the immune response induced by EVLP-G can protect against RABV, mice were challenged with 100 × IMLD50 RABV street strain (Figure 7). All mice mock immunized with PBS died of rabies within nine days of exposure to RABV challenge. In the EVLP-immunized group, two mice developed typical clinical symptoms of rabies and were humanely sacrificed at 12 days after infection, resulting in a 75% survival in that group. However, all mice from EVLP-G group were successfully protected against the high dose RABV challenge, and no clinical signs of rabies were observed in these mice during the 21-day observation period. RABV antigens were detected in the brains of mice that died from the challenge. The results of challenge experiment demonstrated that the immune responses induced by EVLP-G in mice can provide complete protection against a lethal challenge with high dose of RABV street strain.

Bottom Line: The EVLP-G was successfully produced in insect cells by coinfection with three recombinant baculoviruses expressing G, M, and GM-CSF, respectively.EVLP-G was found to induce a significantly increased RABV-specific virus-neutralizing antibody and elicit a larger and broader antibody subclass responses compared with the standard rabies VLP (sRVLP, consisting of G and M).The EVLP-G also elicited significantly more IFN-γ- or IL-4-secreting CD4+ and CD8+ T cells than the sRVLP.

View Article: PubMed Central - PubMed

Affiliation: College of Veterinary Medicine, South China Agricultural University, 483 Wushan Road, Guangzhou 510642, China. kang1989462@sina.com.

ABSTRACT
Rabies remains an important public health threat in most developing countries. To develop a more effective and safe vaccine against rabies, we have constructed a chimeric rabies virus-like particle (VLP), which containing glycoprotein (G) and matrix protein (M) of rabies virus (RABV) Evelyn-Rokitnicki-Abelseth (ERA) strain, and membrane-anchored granulocyte-macrophage colony-stimulating factor (GM-CSF), and it was named of EVLP-G. The immunogenicity and protective efficacy of EVLP-G against RABV were evaluated by intramuscular administration in a mouse model. The EVLP-G was successfully produced in insect cells by coinfection with three recombinant baculoviruses expressing G, M, and GM-CSF, respectively. The membrane-anchored GM-CSF possesses a strong adjuvant activity. More B cells and dendritic cells (DCs) were recruited and/or activated in inguinal lymph nodes in mice immunized with EVLP-G. EVLP-G was found to induce a significantly increased RABV-specific virus-neutralizing antibody and elicit a larger and broader antibody subclass responses compared with the standard rabies VLP (sRVLP, consisting of G and M). The EVLP-G also elicited significantly more IFN-γ- or IL-4-secreting CD4+ and CD8+ T cells than the sRVLP. Moreover, the immune responses induced by EVLP-G protect all vaccinated mice from lethal challenge with RABV. These results suggest that EVLP-G has the potential to be developed as a novel vaccine candidate for the prevention and control of animal rabies.

Show MeSH
Related in: MedlinePlus