Dudareva M, Andrews L, Gilbert S C, Bejon P, Marsh K, Mwacharo J, Kai O, Nicosia A, Hill A V S
Vaccine. 2009 Jun 2;27(27):3501-4. doi: 10.1016/j.vaccine.2009.03.080. Epub 2009 Apr 16.
Vaccination against Plasmodium falciparum malaria could reduce the worldwide burden of this disease, and decrease its high mortality in children. Replication-defective recombinant adenovirus vectors carrying P. falciparum epitopes may be useful as part of a vaccine that raises cellular immunity to the pre-erythrocytic stage of malaria infection. However, existing immunity to the adenovirus vector results in antibody-mediated neutralization of the vaccine vector, and reduced vaccine immunogenicity. Our aim was to examine a population of children who are at risk from P. falciparum malaria for neutralizing immunity to replication-deficient recombinant chimpanzee adenovirus 63 vector (AdC63), compared to human adenovirus 5 vector (AdHu5). We measured 50% and 90% vector neutralization titers in 200 individual sera, taken from a cohort of children from Kenya, using a secreted alkaline phosphatase neutralization assay. We found that 23% of the children (aged 1-6 years) had high-titer neutralizing antibodies to AdHu5, and 4% had high-titer neutralizing antibodies to AdC63. Immunity to both vectors was age-dependent. Low-level neutralization of AdC63 was significantly less frequent than AdHu5 neutralization at the 90% neutralization level. We conclude that AdC63 may be a useful vector as part of a prime-boost malaria vaccine in children.
接种针对恶性疟原虫疟疾的疫苗可减轻全球该疾病的负担,并降低其在儿童中的高死亡率。携带恶性疟原虫表位的复制缺陷型重组腺病毒载体,作为能增强对疟疾感染前红细胞期细胞免疫的疫苗的一部分可能会有用。然而,现有的针对腺病毒载体的免疫力会导致抗体介导的疫苗载体中和作用,并降低疫苗的免疫原性。我们的目的是检查一群有感染恶性疟原虫疟疾风险的儿童,与人类腺病毒5载体(AdHu5)相比,他们对复制缺陷型重组黑猩猩腺病毒63载体(AdC63)的中和免疫力。我们使用分泌性碱性磷酸酶中和试验,测量了从肯尼亚一组儿童采集的200份个体血清中的50%和90%载体中和滴度。我们发现,23%的儿童(年龄在1至6岁之间)对AdHu5有高滴度中和抗体,4%的儿童对AdC63有高滴度中和抗体。对两种载体的免疫均与年龄有关。在90%中和水平时,AdC63的低水平中和明显比AdHu5中和的频率低。我们得出结论,AdC63作为儿童初免-加强疟疾疫苗的一部分可能是一种有用的载体。