Nilsson Charlotta, Sutter Gerd, Walther-Jallow Lilian, Ten Haaft Peter, Åkerblom Lennart, Heeney Jonathan, Erfle Volker, Böttiger Per, Biberfeld Gunnel, Thorstensson Rigmor
Swedish Institute for Infectious Disease Control and Microbiology and Tumor Biology Center, Karolinska Institute, SE-171 82 Solna, Sweden1.
Institute for Molecular Virology, GSF - National Research Centre for Environment and Health, Trogerstr. 4b, 81675 Munich, Germany2.
J Gen Virol. 2002 Apr;83(Pt 4):807-818. doi: 10.1099/0022-1317-83-4-807.
In the present study, the immunogenicity and protective efficacy of a recombinant vaccinia virus-based simian immunodeficiency virus (SIV) vaccine, given alone or in combination with a protein boost, were investigated. Cynomolgus macaques were immunized intramuscularly with modified vaccinia virus Ankara (MVA) expressing the SIVsm env and gag-pol genes (MVA-SIVsm) at 0 and 3 months (n=4), at 0, 3 and 8 months (n=4) or at 0 and 3 months followed by purified native SIVsm gp148 and recombinant SIVmac p27 in immunostimulatory complexes at 8 months (n=4). One month after the last immunization, the vaccinees, together with four naive control monkeys and four monkeys immunized with wild-type MVA, were challenged intrarectally with 10 MID50 SIVsm. At the time of challenge, antibody titres to SIV Env and lymphocyte proliferation responses to whole viral antigen were highest in vaccinees receiving MVA-SIVsm in combination with protein immunizations. Following rectal challenge, one of these vaccinees was completely protected. A prolonged survival time was observed in two of four monkeys in each of the groups immunized with MVA-SIVsm, in two monkeys given MVA-SIVsm followed by protein and in three of four monkeys given wild-type MVA, compared with naive controls. In conclusion, one monkey given the combined vaccine was protected completely against SIVsm infection. Furthermore, immunization with MVA-SIVsm, as well as wild-type MVA alone, seemed to delay disease progression after mucosal SIV infection in a proportion of the monkeys.
在本研究中，对一种基于重组痘苗病毒的猴免疫缺陷病毒（SIV）疫苗单独使用或与蛋白加强免疫联合使用时的免疫原性和保护效力进行了研究。食蟹猴在0个月和3个月时（n = 4）、0个月、3个月和8个月时（n = 4）或0个月和3个月时肌肉注射表达SIVsm env和gag-pol基因的安卡拉改良痘苗病毒（MVA）（MVA-SIVsm），或在0个月和3个月时肌肉注射MVA-SIVsm，随后在8个月时用免疫刺激复合物中的纯化天然SIVsm gp148和重组SIVmac p27进行免疫（n = 4）。最后一次免疫后1个月，将接种疫苗的动物与4只未免疫的对照猴和4只接种野生型MVA的猴一起经直肠用10个50%感染剂量（MID50）的SIVsm进行攻击。在攻击时，接受MVA-SIVsm联合蛋白免疫的接种疫苗动物中，针对SIV Env的抗体滴度和对全病毒抗原的淋巴细胞增殖反应最高。经直肠攻击后，其中一只接种疫苗的动物得到完全保护。与未免疫的对照相比，在接种MVA-SIVsm的每组4只猴中有2只、接种MVA-SIVsm后再接种蛋白的2只猴以及接种野生型MVA的4只猴中有3只观察到生存时间延长。总之，一只接种联合疫苗的猴对SIVsm感染得到完全保护。此外，用MVA-SIVsm以及单独用野生型MVA免疫似乎在一部分猴中延迟了黏膜SIV感染后的疾病进展。
