Vaccination with heat-killed Leishmania antigen or recombinant leishmanial protein and CpG oligodeoxynucleotides induces long-term memory CD4+ and CD8+ T cell responses and protection against Leishmania major infection
Vaccination with heat-killed Leishmania antigen or recombinant leishmanial protein and CpG oligodeoxynucleotides induces long-term memory CD4+ and CD8+ T cell responses and protection against Leishmania major infection
复制标题
DOI：
10.1084/jem.20020147
复制
发表时间：
2002-06-17
影响因子：
15.3
通讯作者：
Seder, RA
中科院分区：
文献类型：
--
作者：
Rhee, EG;Mendez, S;Seder, RA
CpG寡脱氧核苷酸（CpG oligodeoxynucleotides，ODN）在天然和适应性细胞免疫反应中具有重要作用。在这份报告中，CpG ODN的能力，赋予长期的免疫和保护，当用作疫苗佐剂与临床级的利什曼原虫抗原，高压灭菌的利什曼原虫（ALM），或重组利什曼原虫蛋白进行了研究。在两种不同的L.主要感染，接种ALM加CpG ODN能够分别控制易感BALB/c和抗性C57 BL/6（B6）小鼠的感染并显著减少病变发展，直至免疫后12周。此外，用ALM加CpG ODN免疫的136只小鼠即使在接种后6个月仍能抵抗感染性攻击。在保护的免疫相关性方面，ALM加CpG ODN接种的小鼠显示L.主要特异性T辅助细胞I和CD 8（+）应答;另外。在接种疫苗时CD 8（+）T细胞耗竭的小鼠中，完全保护作用明显消失。同样，用重组利什曼原虫蛋白加CpG ODN接种的小鼠也具有依赖于体内CD 8（+）T细胞的长期保护作用。总之，这些数据表明，CpG ODN，当用作疫苗佐剂与重组蛋白或热灭活的利什曼原虫抗原，可以诱导长期保护细胞内感染的CDS依赖性的方式。
CpG oligodeoxynucleotides (ODN) have potent effects on innate and adaptive cellular immune responses,. In this report, the ability, of CpG ODN to confer long-term immunity and protection when used as a vaccine adjuvant with a clinical grade of leishmanial antigen, autoclaved Leishmania major (ALM), or a recombinant leishmanial protein was studied. In two different Mouse models of L. major infection, vaccination with ALM plus CpG ODN was able to control infection and markedly reduce lesion development in susceptible BALB/c and resistant C57BL/6 (B6) mice, respectively, up to 12 wk after immunization. Moreover, 136 mice immunized with ALM plus CpG ODNs were still protected against infectious challenge even 6 mo after vaccination. In terms of immune correlates of protection, ALM plus CpG ODN-vaccinated mice displayed L. major-specific T helper cell I and CD8(+) response,;. In addition. complete protection was markedly abrogated in mice depleted of CD8(+) T cells at the time of vaccination. Similarly, mice vaccinated with a recombinant leishmanial protein plus CpG ODN also had long-term protection that was dependent on CD8(+) T cells in vivo. Together, these data demonstrate that CpG ODN, when used as a vaccine adjuvant with either a recombinant protein or heat-killed leishmanial antigen, can induce long-term protection against an intracellular infection in a CDS-dependent manner.