Background:  The role of maternal immunity, including neutralizing antibodies, in perinatal HIV transmission and disease progression is unclear. The goal of this study was to establish an animal model for perinatal transmission in M. nemestrina using pathogenic SHIV_SF162P3 and to examine virological and immunological parameters associated with transmission and progression.

Methods:  To emulate natural transmission, 10 pregnant Macaca nemestrina were infected intravenously with 100 MID₅₀ of SHIV_SF162P3 in mid-gestation. Dams delivered vaginally unless complications arose and infants were allowed to suckle for 6 months post-birth. Dams and infants were followed longitudinally for CD4⁺ T-cell counts, clinical health, viral load, and antiviral immunity. Infant infection was confirmed by presence or absence of SHIV at birth and at subsequent time points through real time DNA PCR and de novo production of IgM and IgG (ELISA) and neutralizing antibodies against SHIV_SF162 and HIV_SF162. HIV env gene diversity in mothers and infants was measured through PCR amplification and sequencing of V1-V5 region of gp120, followed by phylogenetic analyses. 

Results:  Maternal peak viremia ranged between 10⁷ and 10⁸ copies of RNA per mL plasma and resolved to variable post acute levels. Varying levels of maternal Neutralizing antibodies were produced by the time of birth. Little to no diversification of env in gp120 was evident in the dams prior to delivery; thus autologous Neutralizing antibodies matched to the concurrent maternal virus were passively transferred to all infants. One infant was infected in utero and 2 intrapartum or via breast milk, a rate of 33%. Four of 6 uninfected infants were born to dams with plasma viremia between 10⁴ to 10⁷. Infected infants had de novo env-specific IgM, IgG, and neutralizing antibodies. The infant infected in utero failed to control viremia and lost CD4⁺ T cells by 8 weeks post-birth. Infants infected intra- or postpartum had very low levels of viremia, acquired the dominant maternal virus, developed de novo antiviral immunity, and had no signs of disease. 

Conclusions:  Pathogenic SHIV infection of pregnant macaques during the second trimester results in a perinatal transmission rate of only 33%, despite maternal plasma viremia >10⁴ in 55% of mothers. Control of acute and post-acute viremia in infants infected during or after birth suggests that passive transfer of high levels of autologous maternal Neutralizing antibodies can result in highly controlled viremia.

Keywords: Neutralizing antibodies; perinatal transmission; macaque model