Guthrie Alan J, Quan Melvyn, Lourens Carina W, Audonnet Jean-Christophe, Minke Jules M, Yao Jiansheng, He Ling, Nordgren Robert, Gardner Ian A, Maclachlan N James
Equine Research Centre, University of Pretoria, Private Bag X04, Onderstepoort 0110, South Africa.
Vaccine. 2009 Jul 16;27(33):4434-8. doi: 10.1016/j.vaccine.2009.05.044. Epub 2009 May 31.
We describe the development and preliminary characterization of a recombinant canarypox virus vectored (ALVAC) vaccine for protective immunization of equids against African horse sickness virus (AHSV) infection. Horses (n=8) immunized with either of two concentrations of recombinant canarypox virus vector (ALVAC-AHSV) co-expressing synthetic genes encoding the outer capsid proteins (VP2 and VP5) of AHSV serotype 4 (AHSV-4) developed variable titres (<10-80) of virus-specific neutralizing antibodies and were completely resistant to challenge infection with a virulent strain of AHSV-4. In contrast, a horse immunized with a commercial recombinant canarypox virus vectored vaccine expressing the haemagglutinin genes of two equine influenza H3N8 viruses was seronegative to AHSV and following infection with virulent AHSV-4 developed pyrexia, thrombocytopenia and marked oedema of the supraorbital fossae typical of the "dikkop" or cardiac form of African horse sickness. AHSV was detected by virus isolation and quantitative reverse transcriptase polymerase chain reaction in the blood of the control horse from 8 days onwards after challenge infection whereas AHSV was not detected at any time in the blood of the ALVAC-AHSV vaccinated horses. The control horse seroconverted to AHSV by 2 weeks after challenge infection as determined by both virus neutralization and ELISA assays, whereas six of eight of the ALVAC-AHSV vaccinated horses did not seroconvert by either assay following challenge infection with virulent AHSV-4. These data confirm that the ALVAC-AHSV vaccine will be useful for the protective immunization of equids against African horse sickness, and avoids many of the problems inherent to live-attenuated AHSV vaccines.
我们描述了一种重组金丝雀痘病毒载体(ALVAC)疫苗的研发及初步特性,该疫苗用于马属动物针对非洲马瘟病毒(AHSV)感染的保护性免疫。用两种浓度的共表达编码AHSV血清型4(AHSV - 4)外衣壳蛋白(VP2和VP5)的合成基因的重组金丝雀痘病毒载体(ALVAC - AHSV)免疫马匹(n = 8),产生了不同滴度(<10 - 80)的病毒特异性中和抗体,并且对强毒株AHSV - 4的攻击感染完全具有抗性。相比之下,用表达两种马流感H3N8病毒血凝素基因的商业重组金丝雀痘病毒载体疫苗免疫的一匹马对AHSV血清学阴性,感染强毒株AHSV - 4后出现发热、血小板减少以及眶上窝明显水肿,这是非洲马瘟“dikkop”或心脏型的典型症状。在攻击感染后8天起,通过病毒分离和定量逆转录聚合酶链反应在对照马的血液中检测到AHSV,而在接种ALVAC - AHSV疫苗的马的血液中任何时候都未检测到AHSV。通过病毒中和试验和ELISA试验确定,对照马在攻击感染后2周时血清转化为AHSV阳性,而在接种ALVAC - AHSV疫苗的8匹马中,有6匹在感染强毒株AHSV - 4后通过这两种试验均未发生血清转化。这些数据证实,ALVAC - AHSV疫苗将有助于马属动物针对非洲马瘟的保护性免疫,并避免了减毒活AHSV疫苗固有的许多问题。