Wu Xueling, Parast Adam B, Richardson Barbra A, Nduati Ruth, John-Stewart Grace, Mbori-Ngacha Dorothy, Rainwater Stephanie M J, Overbaugh Julie
Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109-1024, USA.
J Virol. 2006 Jan;80(2):835-44. doi: 10.1128/JVI.80.2.835-844.2006.
Maternal passive immunity typically plays a critical role in protecting infants from new infections; however, the specific contribution of neutralizing antibodies in limiting mother-to-child transmission of human immunodeficiency virus type 1 is unclear. By examining cloned envelope variants from 12 transmission pairs, we found that vertically transmitted variants were more resistant to neutralization by maternal plasma than were maternal viral variants near the time of transmission. The vertically transmitted envelope variants were poorly neutralized by monoclonal antibodies b12 [corrected] 2G12, 2F5, and 4E10 individually or in combination. Despite the fact that the infant viruses were among the most neutralization resistant in the mother, they had relatively few glycosylation sites. Moreover, the transmitted variants elicited de novo neutralizing antibodies in the infants, indicating that they were not inherently difficult to neutralize. The neutralization resistance of vertically transmitted viruses is in contrast to the relative neutralization sensitivity of viruses sexually transmitted within discordant couples, suggesting that the antigenic properties of viruses that are favored for transmission may differ depending upon mode of transmission.
母体被动免疫通常在保护婴儿免受新感染方面发挥关键作用;然而,中和抗体在限制母婴传播1型人类免疫缺陷病毒方面的具体作用尚不清楚。通过检查来自12对传播配对的克隆包膜变体,我们发现垂直传播的变体比传播时母体病毒变体对母体血浆中和作用的抵抗力更强。垂直传播的包膜变体单独或联合使用单克隆抗体b12[校正后]、2G12、2F5和4E10时,中和效果较差。尽管婴儿病毒是母亲体内中和抗性最强的病毒之一,但它们的糖基化位点相对较少。此外,传播的变体在婴儿体内引发了新的中和抗体,这表明它们并非本质上难以中和。垂直传播病毒的中和抗性与不和谐夫妻间性传播病毒的相对中和敏感性形成对比,这表明有利于传播的病毒的抗原特性可能因传播方式而异。