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177 Immune Protection Induced by the Infectious Clone of Live-Attenuated EIAV Vaccine Strain against Lethal Challenge of Wild-Type EIAV
B. Jia1, X. He2, X. Fan2, X. Fei1, Z. Liu1, Q. Zhao2, R. Shen1, and Y. Shao*2
1Harbin Veterinary Res. Inst., Chinese Academy of Agriculture Sci., Harbin, China and 2Natl. Ctr. for AIDS Prevention and Control, Chinese Academy of Preventive Med., Beijing, China
Background: A live-attenuated equine infectious leukemia virus (EIAV) vaccine has been developed in China. The vaccine has put the disease under control in China through immunizing more than 70 million horses and donkeys in the last 2 decades. Being 1 of the 7 lentiviruses, the EIAV vaccine is used as a model to study the pathogenesis and the correlates of immune protection of the lentiviruses, which could shed light on HIV vaccine research.
Methods: The infectious clone pFD3 from the Chinese EIAV attenuated vaccine strain was constructed and used to transfect cells. An infectious virus particle (pD9) was obtained in the ninth passage in fetal donkey dermal cells. A second viral strain (pDL2) was obtained after inoculating the pD9 to donkey leukocyte. Four donkeys were inoculated with pD9 and pDL2, respectively. Ten times donkey lethal doses (DLDs) of wild-type EIAV were used to challenge the animals 6 months after immunization.
Results: After immunization, no fever or other clinical symptoms were observed in the control or the immunized animals. The EIAV-specific antibody response was induced in animals inoculated by pDL2 but not by pD9. In immunized animals, a decline of EIAV proviral DNA was detected by nest-PCR and the signal turned negative 5 months after immunization. After challenge, the 2 control donkeys had 5 days of high fever starting at day 12 and died at day 17. Two days of fever had been observed starting at day 12 in 2 animals immunized with pD9. No fever was seen in 2 animals immunized with pDL2. All 4 animals immunized with either pD7 or pDL2 stayed healthy more than 1 month after challenge.
Conclusions: The challenged animals are still being monitored. Experiences obtained from dozens of experiments showed that no animal could survive more than 1 month after such a challenge without immunization with EIAV vaccines. Therefore, at least partial protection, more probably complete protection, has been obtained by vaccine strain(s) derived from the infectious clone of the live-attenuated EIAV vaccine strain. The study showed the possibility to transform a traditional vaccine into a molecular vaccine. The result provides a solid basis for translating the genomic information carried in the only successfully field-used lentivirus vaccines into HIV vaccine design, which is pending in our laboratory.
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