| Abstract: |
To develop immunoprophylaxis regimens against mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission, we established a simian-human immunodeficiency virus (SHIV) model in neonatal macaques that mimics intrapartum mucosal virus exposure (T.W. Baba, J. Koch, E.S. Mittler et al.: AIDS Res Hum Retroviruses 10:351-357, 1994). We protected four neonates from oral SHIV-vpu+ challenge by ante- and postpartum treatment with a synergistic triple combination of immunoglobulin (Ig) G1 human anti-HIV-1 neutralizing monoclonal antibodies (mAbs) (T.W. Baba, V. Liska, R. Hofmann-Lehmann et al.: Nature Med 6:200-206, 2000), which recognize the CD4-binding site of Env, a glycosylation-dependent gp120, or a linear gp41 epitope. Two neonates that received only postpartum mAbs were also protected from oral SHIV-vpu+ challenge, indicating that postpartum treatment alone is sufficient. Next, we evaluated a similar mAb combination against SHIV89.6P, which encodes env of primary HIV89.6. One of four mAb-treated neonates was protected from infection and two maintained normal CD4+ T-cell counts. We conclude that the epitopes recognized by the three mAbs are important determinants for achieving protection. Combination immunoprophylaxis with synergistic mAbs seems promising to prevent maternal HIV-1 transmission in humans. |
| Keywords: |
controlled study; nonhuman; animals; animal experiment; animal model; monoclonal antibody; chimera; antibodies, monoclonal; immunoglobulin g; infant, newborn; antigen recognition; epitope; newborn; glycosylation; pregnancy; acquired immune deficiency syndrome; acquired immunodeficiency syndrome; virus infection; cd4 antigen; immunoglobulin g1; disease models, animal; macaca; simian immunodeficiency virus; macaca mulatta; genetic code; lymphocyte count; virus transmission; hiv infections; human immunodeficiency virus 1; hiv-1; neutralizing antibody; exposure; mucosa; immunoprophylaxis; virus antibody; passive immunization; immunization, passive; provocation test; virus envelope protein; puerperium; primate model; glycoprotein gp 120; humans; male; female; priority journal; article; postpartum period; human immunodeficiency virus (shiv); neutralizing human anti-hiv monoclonal antibodies; rhesus monkeys; simian; glycoprotein gp 41; disease transmission, vertical
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