Centre for Infection and Immunity, Division of Clinical Sciences, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK.
Vaccine. 2011 Feb 4;29(7):1421-30. doi: 10.1016/j.vaccine.2010.12.034. Epub 2010 Dec 25.
Optimum strategies to elicit and maintain antibodies at mucosal portals of virus entry are critical for the development of vaccines against human immunodeficiency virus (HIV). Here we show in non-human primates that a novel regimen of repeated intravaginal delivery of a non-adjuvanted, soluble recombinant trimeric HIV-1(CN54) clade C envelope glycoprotein (gp140) administered in Carbopol gel can prime for B-cell responses even in the absence of seroconversion. Following 3 cycles of repeated intravaginal administration, throughout each intermenses interval, 3 of 4 macaques produced or boosted systemic and mucosally-detected antibodies upon intramuscular immunisation with gp140 formulated in AS01 adjuvant. Reciprocally, a single intramuscular immunisation primed 3 of 4 macaques for antibody boosting after a single cycle of intravaginal immunisation. Virus neutralising activity was detected against clade C and clade B HIV-1 envelopes but was restricted to highly neutralisation sensitive pseudoviruses.
制定最佳策略以在病毒进入的黏膜门户引发和维持抗体对于开发针对人类免疫缺陷病毒(HIV)的疫苗至关重要。在这里,我们在非人类灵长类动物中表明,一种新型的重复阴道内给予非佐剂、可溶性重组 HIV-1(CN54)C 型包膜糖蛋白(gp140)的方案,在 Carbopol 凝胶中给予,即使没有血清转换,也可以引发 B 细胞反应。在 3 个周期的重复阴道内给药后,在每个间歇期内,4 只恒河猴中的 3 只在肌肉内免疫接种用 AS01 佐剂配制的 gp140 后产生或增强了系统和黏膜检测到的抗体。相反,单次肌肉内免疫接种可在单个阴道内免疫接种周期后引发 4 只恒河猴中的 3 只进行抗体增强。针对 C 型和 B 型 HIV-1 包膜检测到了病毒中和活性,但仅限于高度中和敏感的假病毒。