Safety and efficacy in geese of a PER.C6-based inactivated West Nile virus vaccine.
Studies were performed with an inactivated vaccine against the mosquito-borne flavivirus, West Nile virus (WNV). The mammalian cell line, PER.C6, was selected as the platform for WNV growth since both the neurovirulent strains NY99 and ISR98 that cause epidemics in humans and high mortality in geese, respectively, could be propagated to high titers (10(9) to 10(10)TCID(50)/ml) on these cells. Based on the high DNA homology of the WNV envelope (E) protein and non-structural protein 5 (NS5), and identical neurovirulence in mice and geese, we concluded that NY99 and ISR98 viruses are closely related and therefore vaccine studies were performed with ISR98 as a model for NY99. A robust challenge model in domestic geese was set up resulting in 100% mortality within 7 days of intracranial challenge with 500 TCID(50) WNV. Geese were used to assess the efficacy and safety of an inactivated WNV vaccine produced on PER.C6 cells. Efficacy studies demonstrated 91.4% (53/58) protection of geese compared to no protection (0/13) in geese receiving a sham vaccine. A follow-up study in 1800 geese showed that the vaccine was safe with a survival rate of 96.6% (95% lower CL 95.7%). Initial studies on the correlates of protection induced by the vaccine indicate an important role for antibodies since geese were protected when injected intra-cranial with a mixture of serum from vaccinated, non-challenged geese and WNV. In all, these results provide a scientific basis for the development of an inactivated WNV vaccine based on NY99 produced on PER.C6 cells for human and equine use.
Samina
Itzchak
I
Kimron Veterinary Institute, PO Box 12, Bet Dagan 50250, Israel.
Havenga
Menzo
M
Koudstaal
Wouter
W
Khinich
Yevgeny
Y
Koldijk
Martin
M
Malkinson
Mertyn
M
Simanov
Michael
M
Perl
Shmuel
S
Gijsbers
Linda
L
Weverling
Gerrit Jan
GJ
Uytdehaag
Fons
F
Goudsmit
Jaap
J
D000818:Animals; D000833:Animals, Suckling; D002460:Cell Line; D005777:Geese / Q000821:virology*; D006801:Humans; D007928:Lethal Dose 50; D051379:Mice; D011201:Poultry Diseases / Q000517:prevention & control* / Q000821:virology; D012160:Retina / Q000166:cytology; D016896:Treatment Outcome; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use*; D014779:Virus Replication; D014901:West Nile Fever / Q000401:mortality / Q000517:prevention & control / Q000662:veterinary* / Q000821:virology; D053060:West Nile Virus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use*; D014902:West Nile virus / Q000276:immunology / Q000502:physiology
D015164:Vaccines, Inactivated; D053060:West Nile Virus Vaccines