Maternal and newborn immunization with a human immunodeficiency virus-1 immunogen in a rodent model

We examined immunization with an inactivated, gp120-depleted human immunodeficiency virus (HIV) antigen in incomplete Freund's adjuvant (IFA), also containing a sequence of immunostimulatory (ISS) DNA, during the last trimester of pregnancy and neonatally in a rat model. Pregnant rats were immunized in the third trimester and their litters were immunized during the newborn period. In addition, litters of rats from non-immunized mothers were immunized during the neonatal period. As another control, pregnant rats were immunized and their litters analysed. Supernants from peripheral blood mononuclear cells (PBMCs) were assayed from newborns at 4 weeks of age for HIV-specific interferon-gamma (IFN-gamma), HIV-specific regulated on activation, normal, T-cell expressed, and secreted (RANTES), and serum for p24 antigen-specific immunoglobulin G (IgG) production. In the animals whose pregnant mothers were immunized and were also immunized during the neonatal period, we observed HIV-specific IFN-gamma production and HIV-specific RANTES production, but weak p24 IgG antibody production. Animals immunized only during the neonatal period developed the highest levels of HIV-specific IFN-gamma production, but somewhat lower levels of HIV-specific RANTES and p24 IgG antibody production. The group of animals whose mothers had received immunizations during the last trimester of pregnancy, but were not immunized during the neonatal period, developed the strongest p24 IgG antibody levels, but little or undetectable HIV-specific IFN-gamma or RANTES production. Neonatal immunization resulted primarily in cell-mediated immune responses, while animals born to mothers who were immunized during the last trimester had primarily an antibody-mediated immune response. Immunization of pregnant animals followed by neonatal immunization resulted in a mixed cell-mediated/antibody type profile in the neonatal animal. Future studies should provide insights into neonatal immunity and potential vaccine approaches to prevent neonatal infection and perinatal transmission.