Identification of non-CSP antigens bearing CD8 epitopes in mice immunized with irradiated sporozoites

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• 作者：Satish Mishra^a ; ^{satish.mishra@nyumc.org} ; Urvashi Rai^b ; Takayuki Shiratsuchi^b ; Xiangming Li^b ; Yannick Vanloubbeeck^c ; Joe Cohen^c ; Ruth S. Nussenzweig^a ; Elizabeth A. Winzeler^d ; ^e ; Moriya Tsuji^b ; Victor Nussenzweig^a
• 关键词：Plasmodium ; Malaria vaccine ; Circumsporozoite protein (CSP) ; Non-CSP antigens
• 刊名：Vaccine
• 出版年：2011
• 出版时间：6 October, 2011
• 年：2011
• 卷：29
• 期：43
• 页码：7335-7342
• 全文大小：1K

文摘

Immunization of BALB/c mice with irradiated sporozoites (IrSp) of Plasmodium yoelii can lead to sterile immunity. The circumsporozoite protein (CSP) plays a dominant role in protection. Nevertheless after hyper-immunization with IrSp, complete protection is obtained in CSP-transgenic BALB/c mice that are T-cell tolerant to the CSP and cannot produce antibodies [CSP-Tg/JhT(??]. This protection is mediated exclusively by CD8⁺ T cells . To identify the non-CSP protective T cell antigens, we studied the properties of 34 P. yoelii sporozoite antigens that are predicted to be secreted and to contain strong Kd-restricted CD8⁺ T cell epitopes. The synthetic peptides corresponding to the epitopes were used to screen for the presence of peptide-specific CD8⁺ T cells secreting interferon-¦Ã (IFN-¦Ã) in splenocytes from CSP-Tg/JhT(?? BALB/c mice hyper immunized with IrSp. However, the numbers of IFN-¦Ã-secreting splenocytes specific for the non-CSP antigen-derived peptides were 20-100 times lower than those specific for the CSP-specific peptide. When mice were immunized with recombinant adenoviruses expressing selected non-CSP antigens, the animals were not protected against challenge with P. yoelii sporozoites although large numbers of CD8⁺ specific T cells were generated.