Immune Responses in Wild-type Mice Against Prion Proteins Induced Using a DNA Prime-Protein Boost Strategy

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• 作者：YanLing  ; HAN^a ;   ; ^b ; Yuan  ; LI^a ; Juan  ; SONG^a ;   ; ^b ; Ying  ; WANG^a ;   ; ^b ; Qi  ; SHI^a ; Cao  ; CHEN^a ; BaoYun  ; ZHANG^a ; Yan  ; GUO^a ; ChaoPing  ; LI^b ;   ; ^{cpli005@126.com} ; Jun  ; HAN^a ;   ; ^{hanjun_sci@yahoo.com.cn} ; XiaoPing  ; DONG^a ;   ; ^{dongxp238@sina.com}[Author vitae]
• 关键词：Prion ; DNA vaccine ; Humoral response ; T-cell response ; Prime-boosting regime
• 刊名：Biomedical and Environmental Sciences
• 出版年：2011
• 出版时间：October 2011
• 年：2011
• 卷：24
• 期：5
• 页码：523-529
• 全文大小：632 K

文摘

Objective

To break immune tolerance to prion (PrP) proteins using DNA vaccines.

Methods

Four different human prion DNA vaccine candidates were constructed based on the pcDNA3.1 vector: PrP-WT expressing wild-type PrP, Ubiq-PrP expressing PrP fused to ubiquitin, PrP-LII expressing PrP fused to the lysosomal integral membrane protein type II lysosome-targeting signal, and PrP-ER expressing PrP locating the ER. Using a prime-boost strategy, three-doses of DNA vaccine were injected intramuscularly into Balb/c mice, followed by two doses of PrP protein. Two weeks after the last immunization, sera and spleens were collected and PrP-specific humoral and cellular immune responses evaluated by ELISA and ELISPOT tests.

Results

Higher levels of serum PrP antibodies were detected in mice vaccinated using the strategy of DNA priming followed by protein boosting. Of these, WT-PrP, Ubiq-PrP, and PrP-LII induced significantly higher humoral responses. ELISPOT tests showed markedly increased numbers of IFN-¦Ã-secreting T cells in mice vaccinated using the strategy of DNA priming followed by protein boosting after stimulation with recombinant PrP23-90 and PrP23-231. PrP-ER induced the strongest T-cell response.

Conclusion

Prion vaccines can break tolerance to PrP proteins and induce PrP-specific humoral and cellular immune responses.