Neutralization Escape Variants of Human Immunodeficiency Virus Type 1 Are Transmitted from Mother to Infant

Abstract

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 biz, 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.

Early development of broadly neutralizing antibodies in HIV-1–infected infants

“…Neutralization assays were performed using TZM-bl cells as previously described 16 . Heat-inactivated plasma samples (56°C, 1hr) were tested using six 2-fold serial dilutions, starting at 1:100.…”

Maternal neutralizing antibodies against a CRF01_AE primary isolate are associated with a low rate of intrapartum HIV-1 transmission

“…Particularly, analyses of the role of passively transferred antibodies should clearly separate cases of intrapartum transmission from in utero transmission: only in cases of intrapartum transmission can we be sure that exposure to the virus occurs in the presence of optimal levels of IgGs. Supporting a role of maternal NAbs in limiting MTCT, several recent molecular studies have shown that viruses transmitted are escape variants resistant to autologous maternal plasma (Dickover et al, 2006; Wu et al, 2006). …”

HIV-1 neutralizing antibodies induced by native-like envelope trimers

“…Here, we have evaluated the immunogenicity of a SOSIP.664 trimer based on the BG505 clade A virus, which was isolated from a 6-week old infant that later developed a bNAb response within ~2 years of infection (7, 8). We have also tested, in less detail, a second SOSIP.664 trimer based on a clade B adult infection founder virus, B41 (30).…”