Mazumder Saumyabrata, Ravindran Rajesh, Banerjee Antara, Ali Nahid
Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India.
Vaccine. 2007 Dec 17;25(52):8771-81. doi: 10.1016/j.vaccine.2007.10.028. Epub 2007 Nov 5.
The difficulty in making successful vaccines against leishmaniasis is partly due to lack of an appropriate adjuvant. Non-coding plasmid DNA (pDNA) bearing immunostimulatory sequences (ISS) is a potent activator of innate immunity, and can thus act as an adjuvant with vaccine antigen. We therefore evaluated the efficacy of pDNA and soluble leishmanial antigens (SLA) to protect against challenge with Leishmania donovani infection. We demonstrate that immunomodulatory activity of pDNA, which potentiated a Th1 immune responses, led to enhanced protection with SLA. Importantly, adding cationic liposomes as vehicle to the antigen, with pDNA either complexed or entrapped within, significantly increased the potentiating effect of pDNA. Further, comparison of the two vaccine formulations demonstrated an impressive increase in the protective efficacy up to two folds when both antigen and pDNA were within the vehicle. Thus, these studies establish the utility of non-coding pDNA bearing ISS as strong promoters of vaccine potency of liposomal antigens especially when co-entrapped with the antigen in cationic liposomes.
研发成功的利什曼病疫苗存在困难，部分原因是缺乏合适的佐剂。携带免疫刺激序列（ISS）的非编码质粒DNA（pDNA）是先天免疫的有效激活剂，因此可作为疫苗抗原的佐剂。因此，我们评估了pDNA和可溶性利什曼原虫抗原（SLA）预防杜氏利什曼原虫感染攻击的效果。我们证明，pDNA的免疫调节活性增强了Th1免疫反应，从而增强了SLA的保护作用。重要的是，将阳离子脂质体作为载体添加到抗原中，pDNA与之复合或包封在其中，显著增强了pDNA的增强作用。此外，对两种疫苗制剂的比较表明，当抗原和pDNA都在载体内时，保护效果显著提高了两倍。因此，这些研究证实了携带ISS的非编码pDNA作为脂质体抗原疫苗效力的强力促进剂的效用，特别是当它与抗原共同包封在阳离子脂质体中时。
