Time dependence of protective post-exposure prophylaxis with human monoclonal antibodies against pathogenic SHIV challenge in newborn macaques.

In a primate model of postnatal virus transmission, we have previously shown that 1 h post-exposure prophylaxis (PEP) with a triple combination of neutralizing monoclonal antibodies (nmAbs) conferred sterilizing protection to neonatal macaques against oral challenge with pathogenic simian-human immunodeficiency virus (SHIV). Here, we show that nmAbs can also partially protect SHIV-exposed newborn macaques against infection or disease, when given as 12 or 24 h PEP, respectively. This work delineates the potential and the limits of passive immunoprophylaxis with nmAbs.

Schistosoma mansoni infection promotes SHIV clade C replication in rhesus macaques.

Objective: To evaluate the hypothesis that parasitic infections that induce T-helper type 2 (Th2) immune responses, such as schistosomiasis, upregulate HIV-1 replication.

Design: The effect of concomitant Schistosoma mansoni infection was tested in a primate model of acute and chronic simian-human immunodeficiency virus (SHIV) infection in rhesus macaques using a novel SHIV strain encoding the R5 env gene of a primary HIV clade C isolate from sub-Saharan Africa.

Methods: S.

Phosphorylation of HIV Nef by cAMP-dependent protein kinase.

Nef, a multifunctional accessory protein of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), is important for disease progression. Nef downmodulates CD4 and MHC class I expression, alters host-cell signal transduction pathways, and enhances viral replication. We have identified a novel interaction between Nef and cAMP-dependent kinase (PKA).

The evolution of fetal and infant mortality review as a public health strategy.

Infant mortality review (IMR), the forerunner of fetal and infant mortality review (FIMR), emerged at the national level in the mid-1980s as a promising method to improve understanding of local factors contributing to infant mortality and to motivate community response. Building on federal efforts to enhance data capacity and early state and local infant mortality case review studies, the federal Maternal and Child Health Bureau (MCHB) initiated its IMR Program in 1988. Key actions taken to refine and diffuse the IMR/FIMR method include forging a public-private partnership between MCHB and the American College of Obstetricians and Gynecologists in 1990 to develop the National Fetal and Infant Mortality Review Program, recruiting prominent leaders to advocate for FIMR, seeding community projects in geographically dispersed states and localities, and routinely reporting best practices information to the field.

Complete protection of neonatal rhesus macaques against oral exposure to pathogenic simian-human immunodeficiency virus by human anti-HIV monoclonal antibodies.

Because milk-borne transmission of human immunodeficiency virus (HIV) diminishes the benefits of perinatal antiviral drug therapy in developing countries, we have developed a new strategy to prevent postnatal and, possibly, intrapartum virus transmission in a primate model. Eight neonatal rhesus macaques were exposed orally to pathogenic simian-human immunodeficiency virus (SHIV); 4 neonates were then given intramuscular postexposure prophylaxis with 3 anti-HIV human neutralizing monoclonal antibodies (nMAbs) with potent cross-clade and cross-group neutralization activity. Untreated infants experienced high viral RNA levels and CD4(+) T-cell losses and died (median survival time, 5.

Convergent evolution of SIV env after independent inoculation of rhesus macaques with infectious proviral DNA.

The env gene of three simian immunodeficiency virus (SIV) variants developed convergent mutations during disease progression in six rhesus macaques. The monkeys had been inoculated with supercoiled plasmids encoding infectious proviruses of SIVmac239 (a pathogenic, wild-type strain), SIVdelta3 (the live attenuated vaccine strain derived from SIVmac239), or SIVdelta3+ (a pathogenic progeny virus that had evolved from SIVdelta3). All six monkeys developed immunodeficiency and progressed to fatal disease.