Kabilan L, Sharma V P, Kaur P, Ghosh S K, Yadav R S, Chauhan V S
Malaria Research Center, Delhi, India.
Infect Immun. 1994 Feb;62(2):685-91. doi: 10.1128/iai.62.2.685-691.1994.
Conserved and variant regions of two blood stage vaccine candidate antigens of Plasmodium falciparum, merozoite surface antigen (MSA-1) and ring-infected erythrocyte surface antigen (Pf155/RESA), have been shown to be immunogenic. However, the relative immunogenicity of these immunogens in different populations has not been studied. The conserved N-terminal region of MSA-1 was investigated for its immunogenicity by studying cellular (T cell) and humoral (B cell) immune responses in P. falciparum-primed individuals, living in malaria-hyperendemic areas (Orissa State, India), where malaria presents an alarming situation. MSA-1-derived synthetic peptides contained sequences that activated T cells to proliferate and release gamma interferon in vitro. There was considerable variation in the responses to different peptides. However, the highest responses (51% [18 of 35] by proliferation and 34% [12 of 35] by gamma interferon release) were obtained with a synthetic hybrid peptide containing sequences from conserved N- and C-terminal repeat regions of MSA-1 and Pf155/RESA, respectively. Antibody reactivities in an enzyme immunoassay of plasma samples from these donors to different peptides used for T-cell activation were heterogeneous. In general, there was poor correlation between DNA synthesis and either gamma interferon release or antibody responses in individual donors, underlining the importance of examining several parameters of T-cell activation to assess the total T-cell responsiveness of a study population to a given antigen. However, the results from our studies suggest that synthetic constructs containing sequences from the N- and C-terminal regions of MSA-1 and Pf155/RESA representing different erythrocytic stages of the P. falciparum parasite are more immunogenic in humans living in malaria-hyperendemic areas of India who have been primed by natural infection.
恶性疟原虫的两种血液期疫苗候选抗原，即裂殖子表面抗原（MSA-1）和环状感染红细胞表面抗原（Pf155/RESA）的保守区和可变区，已被证明具有免疫原性。然而，这些免疫原在不同人群中的相对免疫原性尚未得到研究。通过研究生活在疟疾高度流行地区（印度奥里萨邦）的恶性疟原虫感染个体的细胞（T细胞）和体液（B细胞）免疫反应，对MSA-1保守的N端区域的免疫原性进行了研究，该地区疟疾形势严峻。MSA-1衍生的合成肽包含在体外能激活T细胞增殖并释放γ干扰素的序列。对不同肽的反应存在相当大的差异。然而，分别含有来自MSA-1和Pf155/RESA保守N端和C端重复区域序列的合成杂合肽获得了最高反应（增殖反应为51%[35例中的18例]，γ干扰素释放反应为34%[35例中的12例]）。这些供体血浆样本在酶免疫测定中对用于T细胞激活的不同肽的抗体反应性是异质的。一般来说，个体供体中DNA合成与γ干扰素释放或抗体反应之间的相关性较差，这突出了检查T细胞激活的几个参数以评估研究人群对给定抗原的总T细胞反应性的重要性。然而，我们的研究结果表明，含有代表恶性疟原虫寄生虫不同红细胞阶段的MSA-1和Pf155/RESA N端和C端区域序列的合成构建体，对生活在印度疟疾高度流行地区且已通过自然感染致敏的人群具有更强的免疫原性。
