Hui George, Choe Dan, Hashimoto Caryn
Department of Tropical Medicine and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, 651 Ilalo Street, Honolulu, HI 96813, USA.
Clin Vaccine Immunol. 2008 Aug;15(8):1145-50. doi: 10.1128/CVI.00058-08. Epub 2008 Jun 18.
Immunizations with Plasmodium falciparum MSP1-42 or MSP1-19 induce antibodies that inhibit parasites in vitro, which correlates with in vivo protective immunity by vaccination. We previously showed that several adjuvant formulations can induce anti-MSP1-19 antibodies in interleukin-6, intercellular adhesion molecule 1, CD80, and CD86 knockout (KO) mice and at levels similar to those obtained in the healthy uninfected hosts. Here, we determine whether these immune gene KOs or the immunopotentiating activities of the adjuvants have a more important influence on the induction of parasite-inhibitory anti-MSP1-19 antibodies. Results showed that the biological activities of the anti-MSP1-19 antibodies induced by these adjuvants were not affected by the immune gene KOs. All adjuvant formulations that induced significant inhibitory antibody responses (i.e., >50% inhibition of parasite growth) contained monophosphoryl lipid A (MPL) in emulsion carriers, whereas MPL or emulsion carriers alone were ineffective. The ability to retain vaccine efficacy by the MSP1-19 and adjuvant formulations in the altered immunological background is a valuable and significant attribute in light of many instances of skewed immune status in the targeted vaccine populations.
用恶性疟原虫MSP1-42或MSP1-19进行免疫接种可诱导在体外抑制寄生虫的抗体,这与通过疫苗接种产生的体内保护性免疫相关。我们之前表明,几种佐剂配方可在白细胞介素-6、细胞间黏附分子1、CD80和CD86基因敲除(KO)小鼠中诱导抗MSP1-19抗体,且诱导水平与在未感染的健康宿主中获得的水平相似。在此,我们确定这些免疫基因敲除或佐剂的免疫增强活性对诱导抑制寄生虫的抗MSP1-19抗体是否有更重要的影响。结果表明,这些佐剂诱导的抗MSP1-19抗体的生物学活性不受免疫基因敲除的影响。所有诱导显著抑制性抗体反应(即寄生虫生长抑制>50%)的佐剂配方在乳剂载体中均含有单磷酰脂质A(MPL),而单独的MPL或乳剂载体则无效。鉴于目标疫苗人群中许多免疫状态失衡情况,MSP1-19和佐剂配方在改变的免疫背景下保持疫苗效力的能力是一项有价值且重要的特性。