Infectious Diseases Programme, Queensland Institute of Medical Research, Herston, Queensland, Australia.
PLoS One. 2012;7(8):e40928. doi: 10.1371/journal.pone.0040928. Epub 2012 Aug 24.
Vaccines against many pathogens for which conventional approaches have failed remain an unmet public health priority. Synthetic peptide-based vaccines offer an attractive alternative to whole protein and whole organism vaccines, particularly for complex pathogens that cause chronic infection. Previously, we have reported a promising lipid core peptide (LCP) vaccine delivery system that incorporates the antigen, carrier, and adjuvant in a single molecular entity. LCP vaccines have been used to deliver several peptide subunit-based vaccine candidates and induced high titre functional antibodies and protected against Group A streptococcus in mice. Herein, we have evaluated whether LCP constructs incorporating defined CD4(+) and/or CD8(+) T cell epitopes could induce epitope-specific T cell responses and protect against pathogen challenge in a rodent malaria model. We show that LCP vaccines failed to induce an expansion of antigen-specific CD8(+) T cells following primary immunization or by boosting. We further demonstrated that the LCP vaccines induced a non-specific type 2 polarized cytokine response, rather than an epitope-specific canonical CD8(+) T cell type 1 response. Cytotoxic responses of unknown specificity were also induced. These non-specific responses were able to protect against parasite challenge. These data demonstrate that vaccination with lipid core peptides fails to induce canonical epitope-specific T cell responses, at least in our rodent model, but can nonetheless confer non-specific protective immunity against Plasmodium parasite challenge.
针对许多传统方法无法应对的病原体的疫苗仍然是一个未满足的公共卫生重点。基于合成肽的疫苗为传统的蛋白质和整个生物体疫苗提供了一种有吸引力的替代方案,特别是对于引起慢性感染的复杂病原体。以前,我们已经报道了一种有前途的脂质核心肽(LCP)疫苗传递系统,该系统将抗原、载体和佐剂整合在单个分子实体中。LCP 疫苗已被用于递送几种基于肽亚单位的候选疫苗,并诱导了高滴度的功能性抗体,并在小鼠中预防了 A 组链球菌感染。在此,我们评估了包含定义的 CD4(+)和/或 CD8(+)T 细胞表位的 LCP 构建体是否能够诱导表位特异性 T 细胞反应并在啮齿动物疟疾模型中预防病原体挑战。我们表明,LCP 疫苗在初次免疫或加强免疫后均未能诱导抗原特异性 CD8(+)T 细胞的扩增。我们进一步证明,LCP 疫苗诱导了非特异性 2 型极化细胞因子反应,而不是表位特异性的经典 CD8(+)T 细胞 1 型反应。还诱导了特异性未知的细胞毒性反应。这些非特异性反应能够抵御寄生虫的挑战。这些数据表明,用脂质核心肽进行疫苗接种至少在我们的啮齿动物模型中不能诱导经典的表位特异性 T 细胞反应,但仍然可以对疟原虫寄生虫的挑战提供非特异性保护免疫。
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