Medaglini D, Oggioni M R, Pozzi G
Dipartimento di Biologia Molecolare, Università di Siena, Italy.
Am J Reprod Immunol. 1998 Mar;39(3):199-208. doi: 10.1111/j.1600-0897.1998.tb00354.x.
Many viral and bacterial pathogens enter the body through the genital mucosa. Therefore, one of the major goals of a vaccine against sexually transmitted diseases (STDs) should be to induce an immune response in the genital mucosa capable of controlling the entry of the pathogen. Our approach for the development of vaccines against STDs is based on the use of nonpathogenic Gram-positive bacteria as live vaccine vectors.
Recombinant Gram-positive bacteria expressing vaccine antigens were constructed using genetic systems developed in our laboratory. Balb/c mice and Cynomolgus monkeys were inoculated by the vaginal route and vaginal samples were collected using absorbent wicks. Colonization was evaluated by the presence of recombinant bacteria in the vaginal samples. Local and systemic immune responses were studied.
We have developed genetic systems for the expression of heterologous antigens on the surface of the human commensals Streptococcus gordonii and Lactobacillus spp. Both S. gordonii and L. casei stably colonized the murine vagina after a single inoculum. Vaginal colonization of mice with recombinant strains of S. gordonii, expressing human papillomavirus (HPV) and human immunodeficiency virus (HIV) antigens, induced antigen-specific vaginal immunoglobulin A (IgA) and serum IgG. Local and systemic immune responses also were detected in monkeys immunized intravaginally with recombinant S. gordonii.
The results obtained indicated that the approach of using colonizing Gram-positive bacteria as live vectors has a great potential for the development of vaccines against STDs.
许多病毒和细菌病原体通过生殖黏膜进入人体。因此，预防性传播疾病（STD）疫苗的主要目标之一应该是在生殖黏膜中诱导能够控制病原体进入的免疫反应。我们开发预防性传播疾病疫苗的方法是基于使用非致病性革兰氏阳性细菌作为活疫苗载体。
使用我们实验室开发的遗传系统构建表达疫苗抗原的重组革兰氏阳性细菌。通过阴道途径接种Balb/c小鼠和食蟹猴，并使用吸水芯收集阴道样本。通过阴道样本中重组细菌的存在来评估定殖情况。研究局部和全身免疫反应。
我们已经开发出用于在人共生菌戈登链球菌和乳酸杆菌属表面表达异源抗原的遗传系统。单次接种后，戈登链球菌和干酪乳杆菌都能在小鼠阴道中稳定定殖。用表达人乳头瘤病毒（HPV）和人免疫缺陷病毒（HIV）抗原的戈登链球菌重组菌株对小鼠进行阴道定殖，可诱导抗原特异性阴道免疫球蛋白A（IgA）和血清IgG。在用重组戈登链球菌进行阴道免疫的猴子中也检测到了局部和全身免疫反应。
获得的结果表明，使用定殖革兰氏阳性细菌作为活载体的方法在开发预防性传播疾病疫苗方面具有巨大潜力。
