Devi Yengkhom Sangeeta, Mukherjee Paushali, Yazdani Syed Shams, Shakri Ahmad Rushdi, Mazumdar Suman, Pandey Sunita, Chitnis Chetan E, Chauhan Virander S
Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), P.O. Box 10504, Aruna Asaf Ali Marg, New Delhi 110067, India.
Vaccine. 2007 Jul 9;25(28):5166-74. doi: 10.1016/j.vaccine.2007.04.080. Epub 2007 May 21.
An effective malaria vaccine will probably require the delivery of multiple antigens that induce several layers of immunity. Malaria antigens expressed on the surface and in apical organelles of blood-stage merozoites are potential vaccine candidates given their importance in the invasion of erythrocytes. The present study examined the kinetics of humoral response in BALB/c mice following immunization with combination of two blood-stage Plasmodium vivax invasion related molecules, the N-terminal, cysteine-rich region II of P. vivax Duffy binding protein (PvRII) and the 19kDa C-terminal region of merozoite surface protein 1 (PvMSP1(19)) formulated with Montanide ISA 720 and alhydrogel. Immunization with combination of recombinant PvRII and PvMSP1(19) formulated with the Montanide ISA 720 elicited higher antibody titer compared to the alhydrogel formulation. In case of both the adjuvants tested, combination of PvRII and PvMSP1(19) did not result in suppression of antibody response against either antigen when compared to immunization with individual antigens alone. Analysis of IgG subclasses showed that combination of both the recombinant proteins induced a mixed Th1/Th2-type response with almost all IgG subtypes being expressed in equivalent amount. Antibodies elicited against PvRII showed significant inhibitory effect on the binding of PvRII to recombinant Duffy antigen receptor for chemokines (DARC) in an in vitro binding assay. The results of the present study provide a rationale for a combination vaccine against P. vivax malaria based on PvMSP1(19) and PvRII.
一种有效的疟疾疫苗可能需要递送多种抗原,以诱导多层免疫。鉴于血期裂殖子表面和顶端细胞器上表达的疟疾抗原在红细胞入侵中具有重要作用,它们是潜在的疫苗候选物。本研究检测了BALB/c小鼠在用两种与间日疟原虫血期入侵相关分子(间日疟原虫达菲结合蛋白(PvRII)富含半胱氨酸的N端区域II和裂殖子表面蛋白1(PvMSP1(19))的19kDa C端区域)与Montanide ISA 720和氢氧化铝凝胶混合制剂免疫后的体液反应动力学。与氢氧化铝凝胶制剂相比,用重组PvRII和PvMSP1(19)与Montanide ISA 720混合制剂免疫可引发更高的抗体滴度。在测试的两种佐剂中,与单独用单个抗原免疫相比,PvRII和PvMSP1(19)的组合均未导致针对任一抗原的抗体反应受到抑制。IgG亚类分析表明,两种重组蛋白的组合诱导了混合的Th1/Th2型反应,几乎所有IgG亚型的表达量相当。在体外结合试验中,针对PvRII产生的抗体对PvRII与重组趋化因子达菲抗原受体(DARC)的结合具有显著抑制作用。本研究结果为基于PvMSP1(19)和PvRII的间日疟联合疫苗提供了理论依据。