Dereuddre-Bosquet Nathalie, Baron Marie-Laurence, Contreras Vanessa, Gosse Leslie, Mangeot Isabelle, Martinon Frédéric, Yousfi Rahima, Clayette Pascal, Levy Yves, Le Grand Roger
CEA, Division of Immuno-Virology, IDMIT Center, iMETI/DSV, Fontenay-aux-Roses, France; UMR-1184, Université Paris Sud 11, Orsay, France; Vaccine Research Institute (VRI), Créteil, France.
CEA, Division of Immuno-Virology, IDMIT Center, iMETI/DSV, Fontenay-aux-Roses, France; UMR-1184, Université Paris Sud 11, Orsay, France; Vaccine Research Institute (VRI), Créteil, France; INSERM, Paris, France.
Vaccine. 2015 May 11;33(20):2354-9. doi: 10.1016/j.vaccine.2015.03.032. Epub 2015 Apr 1.
We evaluated the immunogenicity of a prime/boost vaccine strategy combining 5 lipopeptides (HIV-Lipo-5) and a recombinant modified vaccinia virus Ankara (rMVA-HIV) in cynomolgus macaques. Both of these vaccine components deliver HIV LAI Gag, Pol, and Nef antigens. Systemic and local safety was excellent in all groups. Immunization with HIV-Lipo-5 alone induced significant serum anti-HIV antibody titers which were not modified by rMVA-HIV immunization. However, induction of T-cell responses, as measured by IFNγ and IL-2 producing cells upon short-term stimulation with HIV peptide pools, required combined immunization with rMVA-HIV. Responses were preferentially observed against Gag antigen. Interestingly, HIV-Lipo-5 efficiently primed HIV induced T-cell responses upon the injection of rMVA-HIV, which may help to reduce the required number of vector injections. Our results provide a rationale for the use of a strategy involving HIV-Lipo-5 priming followed by rMVA-HIV booster immunization as a prophylactic or therapeutic vaccine approach against HIV infection and AIDS.
我们在食蟹猴中评估了一种初免/加强疫苗策略的免疫原性,该策略将5种脂肽(HIV-Lipo-5)与重组改良安卡拉痘苗病毒(rMVA-HIV)相结合。这两种疫苗成分均递送HIV LAI Gag、Pol和Nef抗原。所有组的全身和局部安全性都非常好。单独用HIV-Lipo-5免疫可诱导出显著的血清抗HIV抗体滴度,而rMVA-HIV免疫并未改变这些滴度。然而,通过用HIV肽库进行短期刺激后产生IFNγ和IL-2的细胞来衡量,T细胞反应的诱导需要rMVA-HIV联合免疫。反应优先针对Gag抗原。有趣的是,在注射rMVA-HIV后,HIV-Lipo-5能有效地启动HIV诱导的T细胞反应,这可能有助于减少所需的载体注射次数。我们的结果为使用一种策略提供了理论依据,该策略包括先用HIV-Lipo-5进行初免,然后用rMVA-HIV进行加强免疫,作为预防或治疗HIV感染和艾滋病的疫苗方法。