Rosati Margherita, Alicea Candido, Kulkarni Viraj, Virnik Konstantin, Hockenbury Max, Sardesai Niranjan Y, Pavlakis George N, Valentin Antonio, Berkower Ira, Felber Barbara K
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA.
Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA.
Vaccine. 2015 Apr 27;33(18):2167-74. doi: 10.1016/j.vaccine.2015.02.067. Epub 2015 Mar 21.
Live-attenuated rubella vaccine strain RA27/3 has been demonstrated to be safe and immunogenic in millions of children. The vaccine strain was used to insert SIV gag sequences and the resulting rubella vectors were tested in rhesus macaques alone and together with SIV gag DNA in different vaccine prime-boost combinations. We previously reported that such rubella vectors induce robust and durable SIV-specific humoral immune responses in macaques. Here, we report that recombinant rubella vectors elicit robust de novo SIV-specific cellular immune responses detectable for >10 months even after a single vaccination. The antigen-specific responses induced by the rubella vector include central and effector memory CD4(+) and CD8(+) T cells with cytotoxic potential. Rubella vectors can be administered repeatedly even after vaccination with the rubella vaccine strain RA27/3. Vaccine regimens including rubella vector and SIV gag DNA in different prime-boost combinations resulted in robust long-lasting cellular responses with significant increase of cellular responses upon boost. Rubella vectors provide a potent platform for inducing HIV-specific immunity that can be combined with DNA in a prime-boost regimen to elicit durable cellular immunity.
减毒活风疹疫苗株RA27/3已在数百万儿童中证明是安全且具有免疫原性的。该疫苗株被用于插入猴免疫缺陷病毒(SIV)gag序列,并且所产生的风疹载体在恒河猴中单独进行了测试,还与SIV gag DNA以不同的疫苗初免 - 加强组合进行了测试。我们之前报道过,此类风疹载体在猕猴中可诱导强烈且持久的SIV特异性体液免疫反应。在此,我们报道重组风疹载体即使在单次接种后也能引发强大的、从头开始的SIV特异性细胞免疫反应,这种反应在超过10个月的时间里都可检测到。风疹载体诱导的抗原特异性反应包括具有细胞毒性潜能的中枢和效应记忆CD4(+)和CD8(+) T细胞。即使在接种风疹疫苗株RA27/3后,风疹载体也可重复给药。包含风疹载体和SIV gag DNA的不同初免 - 加强组合的疫苗方案可导致强大且持久的细胞反应,加强免疫后细胞反应显著增加。风疹载体为诱导HIV特异性免疫提供了一个有效的平台,可在初免 - 加强方案中与DNA联合使用以引发持久的细胞免疫。