NEUTRALIZING ANTIBODIES AND VIRAL CHARACTERISTICS IN MOTHER-TO-CHILD TRANSMISSION OF HIV-1

Objective: To determine viral characteristics and the protective effect of virus neutralizing antibodies in mother-to-child transmission of HIV-1. Molecular studies: Ten HIV-1-infected mother-child pairs were sampled within 4 months of delivery. Variable region 3 of the viral envelope was amplified by nested polymerase chain reaction and sequenced, directly and/or after cloning, by solid-phase DNA sequencing. The amino acid sequence of variable region 3 from all 10 children was homogeneous, whereas the mothers showed varying degrees of heterogeneity. Apparently, selection of an HIV-1 variant occurs either at transmission or during initial virus replication in the infected child. No characteristic molecular features of the transmitted virus were identified. Biological studies: Virus isolates from 13 mother-child pairs were characterized for replicative capacity in a variety of cell lines. Eight mothers from whom a virus with a slow/low replicative pattern was isolated transmitted the slow/low virus to their children, whereas mothers with a rapid/high virus transmitted either a rapid/high or a slow/low virus (two cases each). This indicates that viruses with rapid/high replicative capacity do not have a selective advantage during transmission. Virus neutralizing: Sera from 20 mothers were characterized for the ability to neutralize their own virus (autologous neutralization) and virus from other mothers (heterologous neutralization). The results showed that non-transmitting mothers had neutralizing antibodies against autologous virus more frequently than transmitting mothers. In addition, all mothers with autologous neutralizing antibodies also neutralized at least two heterologous primary isolates. This indicates that a broad neutralizing antibody response may be linked to a lower risk of mother-to-child transmission. Conclusion: On the basis of the variable region 3 loop sequence, HIV-1-infected infants harbour homogenous virus populations. Despite this, no molecular or biological markers for selective transmission could be identified. A maternal neutralizing antibody response with broad specificity may protect the child from HIV-1 infection.