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

Objective: To determine viral characteristics and the protective effec t of virus neutralizing antibodies in mother-to-child transmission of HIV-1. Molecular studies: Ten HIV-1-infected mother-child pairs were s ampled within 4 months of delivery. Variable region 3 of the viral env elope was amplified by nested polymerase chain reaction and sequenced, directly and/or after cloning, by solid-phase DNA sequencing. The ami no acid sequence of variable region 3 from all 10 children was homogen eous, whereas the mothers showed varying degrees of heterogeneity. App arently, selection of an HIV-1 variant occurs either at transmission o r during initial virus replication in the infected child. No character istic molecular features of the transmitted virus were identified. Bio logical studies: Virus isolates from 13 mother-child pairs were charac terized for replicative capacity in a variety of cell lines. Eight mot hers from whom a virus with a slow/low replicative pattern was isolate d transmitted the slow/low virus to their children, whereas mothers wi th a rapid/high virus transmitted either a rapid/high or a slow/low vi rus (two cases each). This indicates that viruses with rapid/high repl icative 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 sh owed that non-transmitting mothers had neutralizing antibodies against autologous virus more frequently than transmitting mothers. In additi on, all mothers with autologous neutralizing antibodies also neutraliz ed at least two heterologous primary isolates. This indicates that a b road neutralizing antibody response may be linked to a lower risk of m other-to-child transmission. Conclusion: On the basis of the variable region 3 loop sequence, HIV-1-infected infants harbour homogenous viru s populations. Despite this, no molecular or biological markers for se lective transmission could be identified. A maternal neutralizing anti body response with broad specificity may protect the child from HIV-1 infection.