U.S. Military Malaria Vaccine Program, Naval Medical Research Center, Silver Spring, MD 20910, USA.
Science. 2011 Oct 28;334(6055):475-80. doi: 10.1126/science.1211548. Epub 2011 Sep 8.
Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8(+) T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8(+), IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.
我们的目标是开发一种疫苗，使其在≥80%的接种者中可持续预防恶性疟原虫（Pf）疟疾。通过蚊子叮咬给予疟原虫孢子（PfSPZ）是唯一被证明可在人类中诱导这种保护的免疫原。这种保护被认为是由肝脏中分泌干扰素-γ（IFN-γ）的 CD8（+）T 细胞介导的。我们报告说，通过皮肤中的针接种给予 80 名志愿者纯化的辐照 PfSPZ 是安全的，但免疫原性和保护性较差。动物研究表明，静脉免疫对于在肝脏中诱导高频率的 PfSPZ 特异性 CD8（+）、IFN-γ产生 T 细胞（非人类灵长类动物、小鼠）并赋予保护（小鼠）至关重要。我们的结果表明，这种疫苗的静脉给药将导致预防 Pf 疟疾感染。
