College of Pharmacy, University of Iowa S228 PHAR, Iowa City, IA 52242, USA.
Biomaterials. 2013 Mar;34(10):2524-9. doi: 10.1016/j.biomaterials.2012.12.030. Epub 2013 Jan 11.
Adenoviruses show promising potential as vectors for cancer vaccines, however, their high immunogenicity can be problematic when it comes to homologous prime-boost strategies. In the studies presented here we show that heterologous prime-boost vaccinations involving ovalbumin (OVA)-antigen-coated microparticles as a prime, and adenovirus encoding OVA (AdOVA) as a boost, were equally as effective as homologous AdOVA prime-boosts at generating OVA-specific CD8(+) T-cell responses, which translated into effective tumor protection. OVA-coated biodegradable poly α-hydroxy acid-based microparticles of varying chemistries, when used as primes in heterologous prime-boost vaccinations, were comparable in terms of promoting OVA-specific CD8(+) T cells as well as providing protection against subsequent tumor challenge. These findings auger well for using poly α-hydroxy acid-based microparticles in prime-boost viral vaccination strategies geared toward the safer, and potentially more efficient, generation of anti-tumor immunity.
腺病毒作为癌症疫苗载体具有很大的潜力，然而，在同源的初免-加强策略中，腺病毒的高免疫原性可能会成为问题。在本研究中，我们发现，涉及卵清蛋白（OVA）-抗原包被微球作为初免，以及编码 OVA 的腺病毒（AdOVA）作为加强的异源初免-加强免疫，与同源的 AdOVA 初免-加强免疫一样，能够有效地产生 OVA 特异性 CD8(+)T 细胞反应，从而有效地保护肿瘤。用作异源初免-加强免疫的初免的具有不同化学性质的 OVA 包被可生物降解的聚α-羟基酸微球，在促进 OVA 特异性 CD8(+)T 细胞以及提供针对随后的肿瘤挑战的保护方面具有可比性。这些发现预示着聚α-羟基酸微球在用于更安全、潜在更有效的抗肿瘤免疫的病毒初免-加强疫苗接种策略中具有很好的应用前景。
