Shahi S, Kumar P, Kamboj K K, Rao D N
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
Southeast Asian J Trop Med Public Health. 1997 Dec;28(4):748-56.
Immunization by peptides based on the repeat sequences of Plasmodium falciparum or P. vivax antigen(s) have shown inconsistent results during clinical trials in humans. This could be attributed to the lack of T-cell help or antigenic polymorphism. Thus, attention has been focused towards the more conserved non-repeat regions. The present study was undertaken to map the antigenic determinant in the vicinity of region II (outside the repeat) of CS protein of P. vivax. The immunogenicity of the peptide was studied alone and after linking with polytuftsin (PT), using alum and Freund's adjuvant, in inbred strains of mice with different genetic backgrounds. The humoral response and antigen induced T-cell proliferation assays clearly demonstrated the immunomodulatory activity of PT. Comparable results were observed with antigen(s) administered either in alum or Freund's adjuvant. The induction of IgG2a and IgG2b antibody isotypes by both, peptide as well as the conjugate, may indicate that the T-helper response involved is of Th1 type. Further the immunofluorescence studies have shown that antibodies recognized the air dried sporozoites of P. cynomolgi. The results thus show that the above sequence has overlapping B and T-cell determinants and that alum can be substituted for Freund's adjuvant in generating an effective immune response.
基于恶性疟原虫或间日疟原虫抗原重复序列的肽免疫在人体临床试验中结果不一致。这可能归因于缺乏T细胞辅助或抗原多态性。因此,注意力已集中在更保守的非重复区域。本研究旨在绘制间日疟原虫CS蛋白区域II(重复序列之外)附近的抗原决定簇。使用明矾和弗氏佐剂,在具有不同遗传背景的近交系小鼠中,单独研究该肽以及与聚毛滴虫素(PT)连接后的免疫原性。体液反应和抗原诱导的T细胞增殖试验清楚地证明了PT的免疫调节活性。在明矾或弗氏佐剂中给予抗原时观察到了类似的结果。肽和缀合物均诱导IgG2a和IgG2b抗体亚型,这可能表明所涉及的T辅助反应是Th1型。此外,免疫荧光研究表明抗体识别食蟹猴疟原虫的空气干燥子孢子。因此,结果表明上述序列具有重叠的B细胞和T细胞决定簇,并且在产生有效免疫反应方面,明矾可以替代弗氏佐剂。