Department of Microbiology, Immunology, and Pathology and the Rocky Mountain Regional Center of Excellence, Colorado State University, Ft. Collins, CO 80523, USA.
Vaccine. 2011 Jul 18;29(32):5304-12. doi: 10.1016/j.vaccine.2011.05.009. Epub 2011 May 19.
Development of effective new mucosal vaccine adjuvants has become a priority with the increase in emerging viral and bacterial pathogens. We previously reported that cationic liposomes complexed with non-coding plasmid DNA (CLDC) were effective parenteral vaccine adjuvants. However, little is known regarding the ability of liposome-nucleic acid complexes to function as mucosal vaccine adjuvants, or the nature of the mucosal immune responses elicited by mucosal liposome-nucleic acid adjuvants. To address these questions, antibody and T cell responses were assessed in mice following intranasal immunization with CLDC-adjuvanted vaccines. The effects of CLDC adjuvant on antigen uptake, trafficking, and cytokine responses in the airways and draining lymph nodes were also assessed. We found that mucosal immunization with CLDC-adjuvanted vaccines effectively generated potent mucosal IgA antibody responses, as well as systemic IgG responses. Notably, mucosal immunization with CLDC adjuvant was very effective in generating strong and sustained antigen-specific CD8(+) T cell responses in the airways of mice. Mucosal administration of CLDC vaccines also induced efficient uptake of antigen by DCs within the mediastinal lymph nodes. Finally, a killed bacterial vaccine adjuvanted with CLDC induced significant protection from lethal pulmonary challenge with Burkholderia pseudomallei. These findings suggest that liposome-nucleic acid adjuvants represent a promising new class of mucosal adjuvants for non-replicating vaccines, with notable efficiency at eliciting both humoral and cellular immune responses following intranasal administration.
开发有效的新型黏膜疫苗佐剂已成为当务之急，因为新兴的病毒和细菌病原体不断增加。我们之前曾报道过，带正电荷的脂质体与非编码质粒 DNA（CLDC）复合后可作为有效的非肠道疫苗佐剂。然而，对于脂质体-核酸复合物作为黏膜疫苗佐剂的能力，以及黏膜脂质体-核酸佐剂引发的黏膜免疫反应的性质，人们知之甚少。为了回答这些问题，我们通过鼻腔内免疫接种 CLDC 佐剂疫苗，在小鼠中评估了抗体和 T 细胞反应。还评估了 CLDC 佐剂对呼吸道和引流淋巴结中抗原摄取、运输和细胞因子反应的影响。我们发现，CLDC 佐剂疫苗黏膜免疫可有效产生强大的黏膜 IgA 抗体反应和全身 IgG 反应。值得注意的是，CLDC 佐剂黏膜免疫可非常有效地在小鼠呼吸道中产生强烈和持续的抗原特异性 CD8(+)T 细胞反应。CLDC 疫苗的黏膜给药还诱导了 DC 对纵隔淋巴结内抗原的有效摄取。最后，用 CLDC 佐剂增强的灭活细菌疫苗可显著预防伯克霍尔德氏菌（Burkholderia pseudomallei）引起的致命性肺挑战。这些发现表明，脂质体-核酸佐剂代表了一类有前途的新型非复制疫苗黏膜佐剂，在鼻腔内给药后可有效诱导体液和细胞免疫反应。
