Naz Rajesh K
Department of Obstetrics and Gynecology, Reproductive Immunology and Molecular Biology Laboratories, The West Virginia University, School of Medicine, Morgantown, West Virginia 26505, USA.
Mol Reprod Dev. 2006 Nov;73(11):1473-9. doi: 10.1002/mrd.20591.
Vaccination of female mice with recombinant fertilization antigen (FA-1) causes a long-term reversible contraceptive effect. Also, a DNA vaccine based upon a dodecamer sequence YLP(12) present in sperm causes a reduction in fertility. In the present study, the effects of FA-1 DNA vaccine alone, and FA-1 and YLP(12) DNA vaccines together were examined. FA-1 495-bp DNA was cloned into pVAX1 vector to prepare the DNA vaccine. Four groups of female mice were immunized intradermally by using a gene gun with FA-1 DNA, FA-1 DNA + YLP(12) DNA, FA-1 DNA + YLP(12) DNA mixed with exogenous synthetic CpG oliogodeoxynucleotide (ODN), or vector DNA alone, respectively. Vaccination with all three formulations caused a significant reduction in fertility, with FA-1 DNA + YLP(12) DNA mixed with exogenous synthetic CpG ODN showing the highest reduction. Vaccination with all three formulations raised antibody response in both the sera as well as locally in the vaginal tract, with ODN mixed group demonstrating the highest titers. There was no antibody response in the mice injected with the vector alone. In sera, the highest titers were obtained for the IgG class for all vaccine formulations followed by the IgA class. In vaginal washing, the highest titers were obtained by the IgA class followed by the IgG class. Within the IgG class, the titers for the IgG2a subclass were significantly greater than the IgG1 subclass. The immunocontraceptive effects were long-lasting over 1 year of the observation period and increased with time. These novel findings indicate that the intradermal immunization with a sperm-specific FA-1 DNA vaccine causes a long-term circulating and local immune response resulting in immunocontraceptive effects in female mice. The anti-fertility effects were enhanced when FA-1 DNA vaccine was combined with YLP(12) DNA vaccine and injected with ODN.
用重组受精抗原（FA-1）对雌性小鼠进行疫苗接种可产生长期可逆的避孕效果。此外，基于精子中存在的十二聚体序列YLP(12)的DNA疫苗可降低生育能力。在本研究中，检测了单独使用FA-1 DNA疫苗以及FA-1和YLP(12) DNA疫苗联合使用的效果。将FA-1 495-bp DNA克隆到pVAX1载体中制备DNA疫苗。四组雌性小鼠分别使用基因枪皮内注射FA-1 DNA、FA-1 DNA + YLP(12) DNA、FA-1 DNA + YLP(12) DNA与外源性合成CpG寡脱氧核苷酸（ODN）混合物或单独的载体DNA进行免疫。用所有三种制剂进行疫苗接种均导致生育能力显著降低，其中FA-1 DNA + YLP(12) DNA与外源性合成CpG ODN混合物的降低幅度最大。用所有三种制剂进行疫苗接种均在血清以及阴道局部引发抗体反应，ODN混合组的抗体滴度最高。单独注射载体的小鼠未产生抗体反应。在血清中，所有疫苗制剂的IgG类抗体滴度最高，其次是IgA类。在阴道冲洗液中，IgA类抗体滴度最高，其次是IgG类。在IgG类中，IgG2a亚类的滴度显著高于IgG1亚类。免疫避孕效果在1年的观察期内持久存在且随时间增加。这些新发现表明，用精子特异性FA-1 DNA疫苗进行皮内免疫可引起长期的循环和局部免疫反应，从而在雌性小鼠中产生免疫避孕效果。当FA-1 DNA疫苗与YLP(12) DNA疫苗联合并与ODN一起注射时，抗生育效果增强。
