Rodríguez Ariane, Mintardjo Ratna, Tax Dennis, Gillissen Gert, Custers Jerome, Pau Maria Grazia, Klap Jaco, Santra Sampa, Balachandran Harikrishnan, Letvin Norman L, Goudsmit Jaap, Radosević Katarina
Crucell Holland BV, PO Box 2048, 2301 CA Leiden, The Netherlands.
Vaccine. 2009 Oct 19;27(44):6226-33. doi: 10.1016/j.vaccine.2009.07.106. Epub 2009 Aug 15.
A vaccine that elicits both specific antibodies and IFN-gamma-producing T cells is required to protect against pre-erythrocytic malaria. Among the most promising approaches to induce such complex immunity are heterologous prime-boost vaccination regimens, in particular ones containing live viral vector. We have demonstrated previously that adenovectors serotype 35 (Ads35) encoding the circumsporozoite (CS) antigen or liver-stage antigen-1 (LSA-1) are highly effective in improving the T-cell responses induced by immunizations with protein-based vaccines in a heterologous prime-boost schedule. Here we evaluated the potential of a heterologous prime-boost vaccination that combines the Ad35.CS vector with the serologically distinct adenovector Ad5.CS, in rhesus macaques, after establishing the potency in mice. We show that the heterologous Ad35.CS/Ad5.CS prime-boost regimen elicits both antibody responses and robust IFN-gamma-producing CD8(+) T-cell responses against the CS antigen. Analysis of the quality of the antibody responses in rhesus macaques, using indirect immunofluorescence assay (IFA) with Plasmodium falciparum-coated slides, demonstrated that this heterologous prime-boost regimen elicits a high titer of antibodies that are able to bind to P. falciparum sporozoites. Level of the IFA response was superior to the response measured with sera of an adult human population living in endemic malaria region. In conclusion, the combination of Ad35.CS, a vaccine based on a rare serotype adenovirus, with Ad5.CS or possibly another adenovector of a distinct serotype, induces a complex immune response that is required for protection against malaria, and is thus a highly promising approach for pediatric vaccination.
要预防红细胞前期疟疾，需要一种能引发特异性抗体和产生干扰素-γ的T细胞的疫苗。诱导这种复杂免疫的最有前景的方法之一是异源初免-加强疫苗接种方案，特别是包含活病毒载体的方案。我们之前已经证明，编码环子孢子（CS）抗原或肝期抗原-1（LSA-1）的35型腺病毒载体（Ads35）在异源初免-加强接种方案中，对于提高基于蛋白质的疫苗免疫诱导的T细胞反应非常有效。在确定了在小鼠中的效力后，我们在此评估了将Ad35.CS载体与血清学上不同的腺病毒载体Ad5.CS相结合的异源初免-加强疫苗接种在恒河猴中的潜力。我们表明，异源Ad35.CS/Ad5.CS初免-加强方案引发了针对CS抗原的抗体反应和强大的产生干扰素-γ的CD8(+) T细胞反应。使用恶性疟原虫包被的玻片进行间接免疫荧光测定（IFA）分析恒河猴中抗体反应的质量，结果表明这种异源初免-加强方案引发了高滴度的能够结合恶性疟原虫子孢子的抗体。IFA反应水平优于生活在疟疾流行地区的成年人群血清所测得的反应。总之，基于罕见血清型腺病毒的疫苗Ad35.CS与Ad5.CS或可能另一种不同血清型的腺病毒载体相结合，可诱导针对疟疾保护所需的复杂免疫反应，因此是一种非常有前景的儿科疫苗接种方法。
