Michelini Zuleika, Negri Donatella R M, Baroncelli Silvia, Catone Stefania, Comini Antonella, Maggiorella Maria T, Sernicola Leonardo, Crostarosa Federica, Belli Roberto, Mancini Maria G, Farcomeni Stefania, Fagrouch Zahra, Ciccozzi Massimo, Rovetto Claudia, Liljestrom Peter, Norley Stephen, Heeney Jonathan, Titti Fausto
Laboratory of Virology, Istituto Superiore Sanità, Rome, Italy.
J Med Primatol. 2004 Oct;33(5-6):251-61. doi: 10.1111/j.1600-0684.2004.00076.x.
The immunogenicity and the protective efficacy of a new polyvalent triple vector (DNA/SFV/MVA) based vaccine against mucosal challenge with pathogenic SIVmac251 were investigated. Cynomolgus monkeys (Macaca fascicularis) were primed intradermally with DNA, boosted twice subcutaneously with recombinant Semliki Forest virus (rSFV) and finally intramuscularly with recombinant Modified Vaccinia Virus Ankara strain (rMVA). Both DNA and recombinant viral vectors expressed SIV proteins (Gag, Pol, Tat, Rev, Nef and Env). The vaccinated monkeys developed T helper proliferative responses to viral antigens after the second immunization while interferon (IFN)-gamma enzyme-linked immunosorbent spot-forming cell assay (ELISPOT) specific responses appeared only after the last boost with rMVA. Upon intrarectal challenge with pathogenic SIVmac251, three of four vaccinated monkeys were either fully protected or exhibited a dramatic reduction of virus replication up to undetectable level. A major contribution to this protective effect appeared to be the anamnestic T-cell IFN-gamma ELISPOT responses to vaccine antigens (Gag, Rev, Tat, Nef) that mirrored the viral clearance. These results underline the efficacy of a multiprotein approach in combination with a triple vector system of antigen delivery.
研究了一种新型多价三联载体（DNA/SFV/MVA）疫苗针对致病性SIVmac251黏膜攻击的免疫原性和保护效果。食蟹猴经皮内注射DNA进行初次免疫，然后用重组塞姆利基森林病毒（rSFV）皮下免疫两次，最后用重组安卡拉痘苗病毒株（rMVA）肌肉注射。DNA和重组病毒载体均表达SIV蛋白（Gag、Pol、Tat、Rev、Nef和Env）。接种疫苗的猴子在第二次免疫后对病毒抗原产生了T辅助细胞增殖反应，而干扰素（IFN）-γ酶联免疫斑点形成细胞测定（ELISPOT）特异性反应仅在最后一次用rMVA加强免疫后出现。在用致病性SIVmac251进行直肠内攻击后，四只接种疫苗的猴子中有三只得到了完全保护，或者病毒复制显著减少至检测不到的水平。这种保护作用的一个主要贡献似乎是对疫苗抗原（Gag、Rev、Tat、Nef）的记忆性T细胞IFN-γ ELISPOT反应，这与病毒清除情况相符。这些结果强调了多蛋白方法与三联载体抗原递送系统相结合的有效性。
