Rationale:Guillain Barre syndrome(GBS)is an acute neurological illness leading to quadriparesis with respiratory involvement.It can be triggered by infections,vaccinations,surgery,trauma,transplantation and drugs.Anti...Rationale:Guillain Barre syndrome(GBS)is an acute neurological illness leading to quadriparesis with respiratory involvement.It can be triggered by infections,vaccinations,surgery,trauma,transplantation and drugs.Anti-rabies cell culture vaccines introduced to overcome the high rate of neurological complications associated with tissue based rabies vaccine,can be very rarely associated with GBS.Patient concerns:A 50-year-old female presented with acute severe upper back pain evolving into pure motor quadriparesis following administration of human diploid cell vaccine for rabies.Diagnosis:Acute motor axonal neuropathy variant of GBS following anti-rabies human diploid cell vaccine.Interventions:Intravenous high dose steroids.Outcomes:Patient recovered completely within 1 month.Lessons:Although anti-rabies cell culture vaccines are highly immunogenic and safe,they are rarely associated with GBS.Clinicians should be aware of this link because prompt diagnosis and treatment can result in complete recovery and avoid complications.展开更多
The upstream process was carried out in an animal component-free medium on Cytodex 1 microcarriers. Recombinant trypsin is a non-animal derived protease used as an alternative to animal-derived trypsin. To inactivate ...The upstream process was carried out in an animal component-free medium on Cytodex 1 microcarriers. Recombinant trypsin is a non-animal derived protease used as an alternative to animal-derived trypsin. To inactivate recombinant trypsin, a soybean trypsin inhibitor (STI) should be added to the medium. A protocol was first tested in T-flasks and then passaged to 500 mL and 3 L spinner flasks. Cell detachment was completed in 10 - 12 min, and 0.4 g/L STI was added to a 3L spinner, and cells were transferred into a 30 L stirred tank bioreactor. On day 5, the cell density had reached its maximum (around 1.8 × 106 cells/mL). At an MOI of 0.3 with serum-free medium conditions, cell infection yielded a maximal rabies virus titer of 1.82 × 10<sup>7</sup> FFU/mL at 5 days. All cell culture conditions and virus growth kinetics in serum-free media were investigated. In conclusion, Vero cells were grown on Cytodex 1 with serum-free media and a high amount of rabies virus was obtained. A mouse challenge was used to determine the immune response to an inactivated rabies virus vaccine candidate. Also, we evaluated inactive rabies vaccine candidate safety, and immunogenicity in mice, sheep, horses, and cattle. We found that no horses, sheep, or cattle who were given vaccine IM at 3.2 IU/dose exhibited any clinical sign of disease and all developed high VNA titers (up to 10.03 IU/mL) by 3 - 4 WPI. After the accelerated stability studies, the lyophilized inactivated rabies vaccine candidate showed enough antigenic potency (2.6 IU/mL) in the mouse challenge test. Also, 18-month long-term stability studies showed enough immune response (1.93 IU/mL) on day 14. The activity of the vaccine candidate showed a good immune response and safety criteria that meet WHO requirements. This is the first pilot-scale mammalian cell-based viral rabies vaccine production study in Türkiye that used microcarriers.展开更多
文摘Rationale:Guillain Barre syndrome(GBS)is an acute neurological illness leading to quadriparesis with respiratory involvement.It can be triggered by infections,vaccinations,surgery,trauma,transplantation and drugs.Anti-rabies cell culture vaccines introduced to overcome the high rate of neurological complications associated with tissue based rabies vaccine,can be very rarely associated with GBS.Patient concerns:A 50-year-old female presented with acute severe upper back pain evolving into pure motor quadriparesis following administration of human diploid cell vaccine for rabies.Diagnosis:Acute motor axonal neuropathy variant of GBS following anti-rabies human diploid cell vaccine.Interventions:Intravenous high dose steroids.Outcomes:Patient recovered completely within 1 month.Lessons:Although anti-rabies cell culture vaccines are highly immunogenic and safe,they are rarely associated with GBS.Clinicians should be aware of this link because prompt diagnosis and treatment can result in complete recovery and avoid complications.
文摘The upstream process was carried out in an animal component-free medium on Cytodex 1 microcarriers. Recombinant trypsin is a non-animal derived protease used as an alternative to animal-derived trypsin. To inactivate recombinant trypsin, a soybean trypsin inhibitor (STI) should be added to the medium. A protocol was first tested in T-flasks and then passaged to 500 mL and 3 L spinner flasks. Cell detachment was completed in 10 - 12 min, and 0.4 g/L STI was added to a 3L spinner, and cells were transferred into a 30 L stirred tank bioreactor. On day 5, the cell density had reached its maximum (around 1.8 × 106 cells/mL). At an MOI of 0.3 with serum-free medium conditions, cell infection yielded a maximal rabies virus titer of 1.82 × 10<sup>7</sup> FFU/mL at 5 days. All cell culture conditions and virus growth kinetics in serum-free media were investigated. In conclusion, Vero cells were grown on Cytodex 1 with serum-free media and a high amount of rabies virus was obtained. A mouse challenge was used to determine the immune response to an inactivated rabies virus vaccine candidate. Also, we evaluated inactive rabies vaccine candidate safety, and immunogenicity in mice, sheep, horses, and cattle. We found that no horses, sheep, or cattle who were given vaccine IM at 3.2 IU/dose exhibited any clinical sign of disease and all developed high VNA titers (up to 10.03 IU/mL) by 3 - 4 WPI. After the accelerated stability studies, the lyophilized inactivated rabies vaccine candidate showed enough antigenic potency (2.6 IU/mL) in the mouse challenge test. Also, 18-month long-term stability studies showed enough immune response (1.93 IU/mL) on day 14. The activity of the vaccine candidate showed a good immune response and safety criteria that meet WHO requirements. This is the first pilot-scale mammalian cell-based viral rabies vaccine production study in Türkiye that used microcarriers.
