Bruna-Romero Oscar, Rocha Carolina D, Tsuji Moriya, Gazzinelli Ricardo T
Laboratory of Immunopathology, Centro de Pesquisas René Rachou, FIOCRUZ, Av Augusto de Lima 1715, Belo Horizonte 30190-002, MG, Brazil.
Vaccine. 2004 Sep 9;22(27-28):3575-84. doi: 10.1016/j.vaccine.2004.03.050.
A major malaria vaccine candidate, the circumsporozoite (CS) protein of Plasmodium, is a pre-erythrocytic stage antigen that is attached to the surface of the sporozoites through a glycosylphosphatidylinositol (GPI) anchor. However, here we show that the motif that signals for glycosylphosphatidylinositol anchor addition interferes with the immunogenicity of this protein and reduces protection in mice upon immunization with a recombinant adenovirus. The presence of the glycosylphosphatidylinositol-anchoring motif sequentially affected total circumsporozoite protein production, cellular distribution, antigen processing and secretion, leading to less effective antigen presentation. Consistently, vaccination with an adenovirus recombinant carrying the anchoring motif-disrupted circumsporozoite gene, resulted in significant increase of the number of interferon-gamma (IFN-gamma) producing T cells and specific IgG2a isotype antibodies, ensuing more effective vaccination. Given that the anchoring motif is highly conserved among different species of Plasmodium, anti-malaria subunit vaccines encoded by recombinant vectors that aim at the induction of strong cellular immunity could maximize immunogenicity by removing anchoring motifs.
疟原虫环子孢子（CS）蛋白是一种主要的疟疾疫苗候选物，它是一种前体红细胞期抗原，通过糖基磷脂酰肌醇（GPI）锚定在子孢子表面。然而，我们在此表明，信号介导糖基磷脂酰肌醇锚定添加的基序会干扰该蛋白的免疫原性，并在用重组腺病毒免疫小鼠后降低保护作用。糖基磷脂酰肌醇锚定基序的存在依次影响环子孢子蛋白的总产量、细胞分布、抗原加工和分泌，导致抗原呈递效果降低。同样，用携带破坏锚定基序的环子孢子基因的腺病毒重组体进行疫苗接种，导致产生干扰素-γ（IFN-γ）的T细胞数量和特异性IgG2a同种型抗体显著增加，从而使疫苗接种更有效。鉴于该锚定基序在不同疟原虫物种中高度保守，旨在诱导强烈细胞免疫的重组载体编码的抗疟疾亚单位疫苗可以通过去除锚定基序来最大化免疫原性。
