ROLE OF IMMUNITY IN MATERNAL-INFANT HIV-1 TRANSMISSION

Factors influencing human immunodeficiency virus type 1 (HIV-1) mother -to-child transmission include both immunological and virological para meters: higher viral loads have been associated with clinical stage of HIV-1-infected individuals as well as higher risk of mother-to-child transmission. Furthermore, we have shown that transmitting mothers mor e frequently harbour HIV-1 isolates with rapid/high syncytium-inducing (SI) biological phenotype than non-transmitting mothers do. Genetical ly homogeneous virus populations have been found in HIV-1-infected chi ldren at birth, in contrast to the heterogeneous virus populations oft en found in their infected mothers. This observation suggests that a f ew virus variants are transmitted or initially are replicating in the child. By comparing the HIV-1 gp 120 V3 region of sequentially obtaine d samples from infected children with samples obtained from their moth ers at delivery we found, however, that multiple variants of HIV-1 wit h different outgrowth kinetics can be transmitted. in addition, we hav e obtained results indicating an impaired ability of the immune respon se to adapt to the sequence evolution of HIV-1 in transmitting mothers , as assessed by measuring serum reactivities to peptides representing selected yet closely related V3 sequences. By analysing the presence of antibodies in maternal serum at delivery, which neutralize autologo us isolates as well as other primary virus isolates, we have indicatio ns that a protective immunity in HIV-1 mother-to-child transmission mi ght exist. Immunotherapy has been assessed in infected adult individua ls by passive immunization with a variety of HIV-1-specific antibody p roducts. Data from these studies indicated a differential response to therapy according to the stage of the disease. Active vaccine strategi es, including envelope glycoproteins, pursued so far in seronegative a dult subjects have shown limitations because broadly neutralizing anti bodies, such as can be found in infected individuals, have not been ev oked. Further investigations are therefore needed to give support for the potential use of either passive and/or active immunization for the prevention of HIV-1 mother-to-child transmission.