Pu R, Coleman J, Omori M, Arai M, Hohdatsu T, Huang C, Tanabe T, Yamamoto J K
Department of Pathobiology, College of Veterinary Medicine, University of Florida, Gainesville, 32611-0880, USA.
AIDS. 2001 Jul 6;15(10):1225-37. doi: 10.1097/00002030-200107060-00004.
To evaluate the immunogenicity and efficacy of an inactivated dual-subtype feline immunodeficiency virus (FIV) vaccine.
Specific-pathogen-free cats were immunized with dual-subtype (subtype A FIV(Pet) and subtype D FIV(Shi)) vaccine and challenged with either in vivo- or in vitro-derived FIV inocula.
Dual-subtype vaccinated, single-subtype vaccinated, and placebo-immunized cats were challenged within vivo-derived heterologous subtype B FIV(Bang) [10--100 50% cat infectious doses (CID(50))], in vivo-derived homologous FIV(Shi)(50 CID(50)), and in vitro- and in vivo-derived homologous FIV(Pet)(20--50 CID(50)). Dual-subtype vaccine immunogenicity and efficacy were evaluated and compared to single-subtype strain vaccines. FIV infection was determined using virus isolation and proviral PCR of peripheral blood mononuclear cells and lymphoid tissues.
Four out of five dual-subtype vaccinated cats were protected against low-dose FIV(Bang) (10 CID(50)) and subsequently against in vivo-derived FIV(Pet) (50 CID(50)) challenge, whereas all placebo-immunized cats became infected. Furthermore, dual-subtype vaccine protected two out of five cats against high-dose FIV(Bang) challenge (100 CID(50)) which infected seven out of eight single-subtype vaccinated cats. All dual-subtype vaccinated cats were protected against in vivo-derived FIV(Pet), but only one out of five single-subtype vaccinated cats were protected against in vivo-derived FIV(Pet). Dual-subtype vaccination induced broad-spectrum virus-neutralizing antibodies and FIV-specific interferon-gamma responses along with elevated FIV-specific perforin mRNA levels, suggesting an increase in cytotoxic cell activities.
Dual-subtype vaccinated cats developed broad-spectrum humoral and cellular immunity which protected cats against in vivo-derived inocula of homologous and heterologous FIV subtypes. Thus, multi-subtype antigen vaccines may be an effective strategy against AIDS viruses.
评估一种灭活双亚型猫免疫缺陷病毒(FIV)疫苗的免疫原性和效力。
将特定病原体-free猫用双亚型(A亚型FIV(Pet)和D亚型FIV(Shi))疫苗进行免疫,并分别用体内或体外来源的FIV接种物进行攻毒。
用双亚型疫苗免疫、单亚型疫苗免疫和安慰剂免疫的猫分别用体内来源的异源B亚型FIV(Bang)[10 - 100个50%猫感染剂量(CID(50))]、体内来源的同源FIV(Shi)(50个CID(50))以及体外和体内来源的同源FIV(Pet)(20 - 50个CID(50))进行攻毒。评估双亚型疫苗的免疫原性和效力,并与单亚型毒株疫苗进行比较。使用病毒分离以及外周血单核细胞和淋巴组织的前病毒PCR来确定FIV感染情况。
五只接受双亚型疫苗免疫的猫中有四只在低剂量FIV(Bang)(10个CID(50))攻毒后得到保护,随后在体内来源的FIV(Pet)(50个CID(50))攻毒中也得到保护,而所有接受安慰剂免疫的猫均被感染。此外,双亚型疫苗在五只猫中保护了两只抵御高剂量FIV(Bang)攻毒(100个CID(50)),而八只接受单亚型疫苗免疫的猫中有七只被感染。所有接受双亚型疫苗免疫的猫在体内来源的FIV(Pet)攻毒中均得到保护,但五只接受单亚型疫苗免疫的猫中只有一只在体内来源的FIV(Pet)攻毒中得到保护。双亚型疫苗接种诱导了广谱病毒中和抗体和FIV特异性干扰素-γ反应,同时FIV特异性穿孔素mRNA水平升高,提示细胞毒性细胞活性增强。
接受双亚型疫苗免疫的猫产生了广谱的体液和细胞免疫,可保护猫抵御体内来源的同源和异源FIV亚型接种物。因此,多亚型抗原疫苗可能是对抗艾滋病病毒的有效策略。