Maggiorella Maria Teresa, Sernicola Leonardo, Crostarosa Federica, Belli Roberto, Pavone-Cossut Maria Rosaria, Macchia Iole, Farcomeni Stefania, Tenner-Racz Klara, Racz Paul, Ensoli Barbara, Titti Fausto
Division of Experimental Retrovirology and Non-Human Primate Models, National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.
J Med Primatol. 2007 Aug;36(4-5):180-94. doi: 10.1111/j.1600-0684.2007.00236.x.
Vaccine combining structural and regulatory proteins is an emerging approach to develop an HIV/AIDS vaccine and therefore, the immunogenicity and efficacy of two regimens of immunization combining structural (Gag/Pol, Env) and regulatory (Rev, Tat, Nef) Simian immunodeficiency virus (SIV) proteins were compared in cynomolgus monkeys.
Monkeys were immunized with Modified Vaccine Ankara vector (MVA-J5) (protocol 1) or with DNA, Semliki forest virus and MVA vectors (DNA/SFV/MVA) (protocol 2). At week 32, all monkeys were challenge intravenously (protocol 1) or intrarectally (protocol 2) with 50 MID(50) of SIVmac251. Humoral, proliferative responses and in particular in protocol 2, the frequency of IFN-gamma producing cells, were measured in all monkeys before and after the challenge.
Both vaccine regimens elicited humoral and proliferative responses but failed to induce neutralizing antibodies. Upon intravenous challenge, two out of three MVA-J5 vaccinated monkeys exhibited a long-term control of the viral replication whereas DNA/SFV/MVA vaccine abrogated the virus replication up to undetectable level in three out of four vaccinated monkeys. A major contribution to this vaccine effect appeared to be the IFN-gamma/ELISPOT responses to vaccine antigens (Gag, Rev Tat and Nef).
These results, indicate that multiprotein heterologous prime-boost vaccination can induce a robust vaccine-induced immunity able to abrogate virus replication.
将结构蛋白和调节蛋白结合的疫苗是开发艾滋病毒/艾滋病疫苗的一种新兴方法，因此，在食蟹猴中比较了两种免疫方案（结合结构蛋白（Gag/Pol、Env）和调节蛋白（Rev、Tat、Nef）的猿猴免疫缺陷病毒（SIV）蛋白）的免疫原性和效力。
用改良安卡拉疫苗载体（MVA-J5）（方案1）或DNA、塞姆利基森林病毒和MVA载体（DNA/SFV/MVA）（方案2）对猴子进行免疫。在第32周时，所有猴子通过静脉注射（方案1）或经直肠注射（方案2）50个50%感染剂量（MID(50)）的SIVmac251进行攻击。在攻击前后，对所有猴子测量体液、增殖反应，特别是在方案2中，测量产生γ干扰素细胞的频率。
两种疫苗方案均引发了体液和增殖反应，但未能诱导出中和抗体。静脉注射攻击后，三只接种MVA-J5的猴子中有两只对病毒复制表现出长期控制，而DNA/SFV/MVA疫苗在四只接种疫苗的猴子中有三只将病毒复制消除到检测不到的水平。对这种疫苗效果的主要贡献似乎是对疫苗抗原（Gag、Rev、Tat和Nef）的γ干扰素/酶联免疫斑点反应。
这些结果表明，多蛋白异源初免-加强免疫接种可诱导强大的疫苗诱导免疫，能够消除病毒复制。
