六种精子肽疫苗免疫对雌性小鼠生育力的影响。

Reproductive Immunology and Molecular Biology Laboratory, Department of Obstetrics and Gynecology, The West Virginia University, School of Medicine, Morgantown, West Virginia 26505, USA.

Soc Reprod Fertil Suppl. 2007;63:455-64.

Spermatozoon is an exciting target for contraceptive vaccine development. Several sperm antigens (native or recombinant) and sperm peptides cause various degrees of contraceptive effect in female mice. No single antigen/ peptide has shown to cause a complete block in fertility in the mouse model. To enhance the efficacy of the vaccine, six sperm peptides were selected for the present study namely mFA-12,19, mFA-1117136, YLP12, P10G, A9D and SP56. These have been shown to cause > 50% to > 80% reduction in fertility when used individually for immunization. The present study was undertaken to test the hypothesis that the vaccination with all the six peptides together will enhance the contraceptive efficacy by an additive effect resulting in a complete block of fertility in the mouse model. Six vaccines were prepared by conjugating the six synthetic peptides with the recombinant binding subunit of cholera toxin (rCTB). Female CD-1 mice were immunized intramuscularly with all the six peptide vaccines. Each animal received a total of five injections at 2- to 3- week intervals of all of the six vaccines and each vaccine was injected at a separate site. Approximately four weeks after the last injection, the animals were mated. Immunization of each mouse with all six peptides resulted in a dose-dependent inhibition of fertility. At 150 micro g dose, there was an overall 45% reduction compared to controls. Several mice produced antibodies (> or = 2SD units) against these peptides in the serum and the genital tract but the titers were low, and many animals did not respond to several peptides. No animal produced antibodies to all six peptides in serum or the genital tract. When the antibody titers against all six peptides disappeared after > 10 months from circulation and the genital tract, all the animals regained fertility. These findings indicate that the immunization with the six sperm peptide vaccines induce antibodies in serum and the genital tract that cause a reversible long-term contraceptive effect in female mice. The inhibition in fertility was up to 45% rather than a complete block that seems to be due to low antibody titers, especially in the genital tract. It was interesting to note that even with such low titers there was a significant reduction in fertility after immunization with multipeptide vaccine. Multipeptide vaccination is an exciting approach and the present preliminary data warrant further studies.

精子是避孕疫苗研发中一个令人关注的靶点。几种精子抗原（天然的或重组的）以及精子肽在雌性小鼠中会产生不同程度的避孕效果。在小鼠模型中，没有单一的抗原/肽能完全阻断生育能力。为提高疫苗的效力，本研究选择了六种精子肽，即mFA-12,19、mFA-1117136、YLP12、P10G、A9D和SP56。单独用于免疫时，这些肽已显示出能使生育能力降低50%至80%以上。本研究旨在验证以下假设：同时用这六种肽进行疫苗接种将通过累加效应提高避孕效力，从而在小鼠模型中完全阻断生育能力。通过将六种合成肽与霍乱毒素的重组结合亚基（rCTB）偶联制备了六种疫苗。雌性CD-1小鼠通过肌肉注射接种所有六种肽疫苗。每只动物总共接受五次注射，六种疫苗每隔2至3周注射一次，且每种疫苗在不同部位注射。最后一次注射约四周后，让动物交配。用所有六种肽对每只小鼠进行免疫导致了生育能力的剂量依赖性抑制。在150微克剂量时，与对照组相比，总体生育能力降低了45%。几只小鼠在血清和生殖道中产生了针对这些肽的抗体（≥2个标准差单位），但滴度较低，而且许多动物对几种肽没有反应。没有动物在血清或生殖道中产生针对所有六种肽的抗体。当针对所有六种肽的抗体滴度在循环和生殖道中超过10个月后消失时，所有动物都恢复了生育能力。这些发现表明，用六种精子肽疫苗进行免疫会在血清和生殖道中诱导产生抗体，从而在雌性小鼠中产生可逆的长期避孕效果。生育能力的抑制高达45%，而非完全阻断，这似乎是由于抗体滴度较低，尤其是在生殖道中。值得注意的是，即使滴度如此之低，用多种肽疫苗免疫后生育能力仍有显著降低。多种肽疫苗接种是一种令人感兴趣的方法，目前的初步数据值得进一步研究。