Parra M, Hui G, Johnson A H, Berzofsky J A, Roberts T, Quakyi I A, Taylor D W
Departments of Biology, Georgetown University, Washington, DC 20057, USA.
Infect Immun. 2000 May;68(5):2685-91. doi: 10.1128/IAI.68.5.2685-2691.2000.
Vaccines for P. falciparum will need to contain both T- and B-cell epitopes. Conserved epitopes are the most desirable, but they are often poorly immunogenic. The major merozoite surface protein 1 (MSP-1) is currently a leading vaccine candidate antigen. In this study, six peptides from conserved or partly conserved regions of MSP-1 were evaluated for immunogenicity in B10 congenic mice. Following immunization with the peptides, murine T cells were tested for the ability to proliferate in vitro and antibody responses to MSP-1 were evaluated in vivo. The results showed that one highly conserved sequence (MSP-1#1, VTHESYQELVKKLEALEDAV; located at amino acid positions 20 to 39) and one partly conserved sequence (MSP-1#23, GLFHKEKMILNEEEITTKGA; located at positions 44 to 63) contained both T- and B-cell epitopes. Immunization of mice with these peptides resulted in T-cell proliferation and enhanced production of antibody to MSP-1 upon exposure to merozoites. MSP-1#1 stimulated T-cell responses in three of the six strains of mice evaluated, whereas MSP-1#23 was immunogenic in only one strain. Immunization with the other four peptides resulted in T-cell responses to the peptides, but none of the resulting peptide-specific T cells recognized native MSP-1. These results demonstrate that two sequences located in the N terminus of MSP-1 can induce T- and B-cell responses following immunization in a murine model. Clearly, these sequences merit further consideration for inclusion in a vaccine for malaria.
恶性疟原虫疫苗需要同时包含T细胞和B细胞表位。保守表位是最理想的，但它们的免疫原性往往较差。主要裂殖子表面蛋白1（MSP-1）目前是主要的候选疫苗抗原。在本研究中，评估了来自MSP-1保守或部分保守区域的六种肽在B10同源小鼠中的免疫原性。用这些肽免疫后，检测小鼠T细胞在体外增殖的能力，并在体内评估对MSP-1的抗体反应。结果表明，一个高度保守序列（MSP-1#1，VTHESYQELVKKLEALEDAV；位于氨基酸位置20至39）和一个部分保守序列（MSP-1#23，GLFHKEKMILNEEEITTKGA；位于位置44至63）同时包含T细胞和B细胞表位。用这些肽免疫小鼠导致T细胞增殖，并在暴露于裂殖子后增强了对MSP-1的抗体产生。MSP-1#1在评估的六种小鼠品系中的三种中刺激了T细胞反应，而MSP-1#23仅在一个品系中具有免疫原性。用其他四种肽免疫导致对这些肽的T细胞反应，但产生的肽特异性T细胞均未识别天然MSP-1。这些结果表明，位于MSP-1 N末端的两个序列在小鼠模型中免疫后可诱导T细胞和B细胞反应。显然，这些序列值得进一步考虑纳入疟疾疫苗。
