Protective antibodies against a sphingomyelinase D from Loxosceles intermedia spider venom elicited in mice with different genetic background

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• 作者：Camila Franco Batista Oliveira^a ; Andrea Vilela^a ; Luis Augusto M. Coura^a ; Fernandes Tenó ; rio Gomes Rodrigues^a ; Ronaldo Alves Pinto Nagem^a ; Carlos Chá ; vez-Olortegui^a ; Tatiani U. Maioli^b ; Liza F. Felicori^a ;
• 关键词：Synthetic peptides ; Loxosceles ; B-cell epitopes ; Vaccination ; Anti-venom ; HLAII transgenic mice
• 刊名：Vaccine
• 出版年：2016
• 出版时间：19 July 2016
• 年：2016
• 卷：34
• 期：33
• 页码：3828-3834
• 全文大小：1144 K

文摘

In the present investigation we used a recombinant LiD1 toxin, named rLiD1his, from Loxosceles intermedia brown spider to elicit specific antibodies in mice carrying different Human Leukocyte Antigens class II (HLAII) {DRB1.0401 (DR4), DQB1.0601 (DQ6) and DQB1.0302 (DQ8)} as well as in BALB/C and C57BL/6 control mice. All mice strains produced high antibody titers against rLiD1his but DR4 mice antibodies (the lower responder mice) were not able to recognize L. intermedia crude venom. The anti-rLiD1his sera, except from DR4 mice, were able to neutralize dermonecrotic, hemorrhagic and edematogenic effects of rLiD1his in naïve rabbits. Overlapping peptides from the amino acid sequence of LiD1 toxin were prepared by SPOT method and differences in LiD1 epitope recognition were observed using different mice anti-rLiD1his sera. The region ¹⁶⁰DKVGHDFSGNDDISDVGK¹⁷⁷ was recognized by transgenic DQ8 and DQ6 mice sera. Other epitopes were recognized by at least two different animals’ sera including ¹⁰MGHMVNAIGQIDEFVNLG²⁷, ³⁷FDDNANPEYTYHGIP⁵¹, ⁷⁰GLRSATTPGNSKYQEKLV⁸⁷ and ²⁵⁹AAYKKKFRVATYDDN²⁷³. Among these epitopes, the epitopes 37–51 and 160–177 have already been shown in previously studies as good candidates to be used alone or combined with other peptides to induce protective immune response against Loxosceles venoms. The results presented here highlight the importance of HLAII in antibody response and recognition of specific B-cell epitopes of rLiD1his spider toxin according to HLAII type and impact in the epitopic vaccine development against this spider.