Ockenhouse C F, Sun P F, Lanar D E, Wellde B T, Hall B T, Kester K, Stoute J A, Magill A, Krzych U, Farley L, Wirtz R A, Sadoff J C, Kaslow D C, Kumar S, Church L W, Crutcher J M, Wizel B, Hoffman S, Lalvani A, Hill A V, Tine J A, Guito K P, de Taisne C, Anders R, Ballou W R
Department of Immunology, Walter Reed Army Institute of Research, Washington, DC 20307, USA.
J Infect Dis. 1998 Jun;177(6):1664-73. doi: 10.1086/515331.
Candidate malaria vaccines have failed to elicit consistently protective immune responses against challenge with Plasmodium falciparum. NYVAC-Pf7, a highly attenuated vaccinia virus with 7 P. falciparum genes inserted into its genome, was tested in a phase I/IIa safety, immunogenicity, and efficacy vaccine trial in human volunteers. Malaria genes inserted into the NYVAC genome encoded proteins from all stages of the parasite's life cycle. Volunteers received three immunizations of two different dosages of NYVAC-Pf7. The vaccine was safe and well tolerated but variably immunogenic. While antibody responses were generally poor, cellular immune responses were detected in >90% of the volunteers. Of the 35 volunteers challenged with the bite of 5 P. falciparum-infected Anopheles mosquitoes, 1 was completely protected, and there was a significant delay in time to parasite patency in the groups of volunteers who received either the low or high dose of vaccine compared with control volunteers.
候选疟疾疫苗未能始终如一地引发针对恶性疟原虫攻击的保护性免疫反应。NYVAC-Pf7是一种高度减毒的痘苗病毒,其基因组中插入了7个恶性疟原虫基因,在一项针对人类志愿者的I/IIa期安全性、免疫原性和有效性疫苗试验中进行了测试。插入NYVAC基因组的疟疾基因编码了寄生虫生命周期各阶段的蛋白质。志愿者接受了两种不同剂量的NYVAC-Pf7的三次免疫接种。该疫苗安全且耐受性良好,但免疫原性存在差异。虽然抗体反应通常较差,但在超过90%的志愿者中检测到了细胞免疫反应。在35名被5只感染恶性疟原虫的按蚊叮咬攻击的志愿者中,1人得到了完全保护,与对照志愿者相比,接受低剂量或高剂量疫苗的志愿者组中,寄生虫出现的时间有显著延迟。