Portocarrero Carla, Markley Karen, Koprowski Hilary, Spitsin Sergei, Golovkin Maxim
Biotechnology Foundation Laboratories, Thomas Jefferson University, Philadelphia, PA 19107-6799, United States.
Vaccine. 2008 Oct 9;26(43):5535-40. doi: 10.1016/j.vaccine.2008.07.063. Epub 2008 Aug 14.
The extracellular virion membrane protein B5 is a potent inducer of immune responses capable of protecting mice and primates against poxvirus infections. Here, we examined the antibody response induced in mice immunized intramuscularly (i.m.) or intranasally (i.n.) with plant-derived B5 (pB5) accompanied or not with plant total soluble protein (TSP) at various concentrations. Increasing amounts of TSP inhibited the pB5-specific response in both i.m.- and i.n.-immunized mice, with more dramatic effects in the latter. pB5 administered to mucosal surfaces induced specific IgG and IgA responses, whereas i.m. immunization produced high serum IgG titers and no IgA. A 6-fold increase in pB5 dosage administered i.n. led to an antibody response comparable to that obtained by i.m. injection. Our study addresses the quality/quantity issues of the pB5 subunit preparation and demonstrates the feasibility of mucosal administration of plant-derived smallpox subunit vaccine in obtaining a potent immune response. Overall, this work points to the practicability of needle-free mucosal administration of such vaccines in light of purity, dosage and adjuvant formulation.
细胞外病毒粒子膜蛋白B5是一种强大的免疫反应诱导剂,能够保护小鼠和灵长类动物免受痘病毒感染。在此,我们检测了用植物源B5(pB5)肌肉注射(i.m.)或鼻内(i.n.)免疫小鼠时,不同浓度植物总可溶性蛋白(TSP)伴随或不伴随pB5所诱导的抗体反应。TSP量的增加抑制了i.m.和i.n.免疫小鼠的pB5特异性反应,对后者的影响更显著。给予黏膜表面的pB5诱导了特异性IgG和IgA反应,而i.m.免疫产生了高血清IgG滴度且无IgA。鼻内给予的pB5剂量增加6倍导致了与i.m.注射相当的抗体反应。我们的研究解决了pB5亚基制剂的质量/数量问题,并证明了黏膜给予植物源天花亚基疫苗以获得有效免疫反应的可行性。总体而言,鉴于纯度、剂量和佐剂配方,这项工作指出了此类疫苗无针黏膜给药的实用性。