ABSTRACT
The murine model was developed to assess the effects of maternally transferred HIV hyperimmune globulin or human intravenous immune globulin on the immunization of the offspring at 18-21 days of age with rgp 120SF2-complete Freund's adjuvant. Either HIV hyperimmune globulin or intravenous immune globulin was administered intraperitoneally to post-partum BALB/c mice and was transferred via milk to the offspring. Both HIV hyperimmune globulin and intravenous immune globulin inhibited the offspring anti-rgp 120SF2 IgG response to the vaccine. The HIV hyperimmune globulin inhibition persisted for 28 days after immunization while the intravenous immune globulin inhibition was still present at 63 days after immunization. In addition, the intravenous immune globulin had a more generalized immunosuppressive effect, inhibiting the IgG response to both rpg 120SF2 and an additional protein antigen, hen egg-white lysozyme. Effects of maternal or exogenously administered pre-existing antibody, including control antibodies (intravenous immune globulin), on the newborn response to HIV and other vaccines must be carefully evaluated when vaccine studies proceed in newborns.
Subject(s)
AIDS Vaccines/pharmacology , HIV Antibodies/pharmacology , Immunity, Maternally-Acquired/drug effects , Immunoglobulins, Intravenous/pharmacology , AIDS Vaccines/immunology , Amino Acid Sequence , Animals , Disease Models, Animal , Female , HIV Envelope Protein gp120/immunology , Humans , Immunoglobulin G/analysis , Immunoglobulin G/drug effects , Mice , Mice, Inbred BALB C , Molecular Sequence DataABSTRACT
Hyperimmune anti-human immunodeficiency virus immunoglobulin (HIVIG) is an intravenous immunoglobulin prepared from HIV-infected asymptomatic donors with a CD4 cell count greater than 400 cells/microl and a high titer of antibody to HIV-1 p24 protein. Twelve persons with AIDS received four doses of HMG (two at 50 mg/kg of body weight and then two at 200 mg/kg) every 28 days. Pharmacokinetics were evaluated by measurement of anti-p24 antibody. HIVIG was well tolerated, and all participants completed the study. Three subjects who were not receiving Pneumocystis carinii pneumonia (PCP) prophylaxis developed PCP. The mean value for HIVIG clearance was 3.02 ml/kg/day at 50 mg/kg and 3.65 ml/kg/day at 200 mg/kg (P = 0.027); the mean trough antibody titers (reciprocal units) were 1,442 and 4,428, respectively. This study indicates that high titers of anti-p24 antibody can be maintained with a monthly administration schedule of HIVIG and that short-term safety is acceptable. Comparisons to evaluate the therapeutic potential of HIVIG are justified.
Subject(s)
Acquired Immunodeficiency Syndrome/immunology , HIV , Immunoglobulins, Intravenous/pharmacokinetics , Adult , Aged , HIV Seropositivity , Half-Life , Humans , Immunoglobulins, Intravenous/adverse effects , Metabolic Clearance RateABSTRACT
The pharmacokinetics and safety of hyperimmune anti-human immunodeficiency virus (HIV) intravenous immunoglobulin (HIVIG) were evaluated in the first 28 maternal-infant pairs enrolled in a randomized, intravenous immunoglobulin (IVIG)-controlled trial of HIVIG maternal-infant HIV transmission prophylaxis. Using 200 mg/kg, mean half-life and volume of distribution (Vd) in women were 15 days and 72 mL/kg, respectively, after one and 32 days and 154 mL/kg after three monthly infusions, with stable 4 mL/kg/day clearance. Transplacental passage occurred. Newborn single-dose half-life, Vd, and clearance were 30 days, 143 mL/kg, and 4 mL/kg/day, respectively. HIVIG rapidly cleared maternal serum immune complex-dissociated p24 antigen, and plasma HIV-1 RNA levels were stable. Mild to moderate adverse clinical effects occurred in 2 of 103 maternal and 2 of 25 infant infusions. No adverse hematologic, blood chemistry, or immunologic effects were seen. HIVIG is well-tolerated in HIV-infected pregnant women and their newborns, clears antigenemia, crosses the placenta, and exhibits pharmacokinetics similar to those of other immunoglobulin preparations.
Subject(s)
HIV Infections/prevention & control , HIV Infections/therapy , Immunoglobulins, Intravenous/pharmacokinetics , Adolescent , Adult , Female , HIV Antibodies/analysis , HIV Core Protein p24/analysis , HIV Core Protein p24/blood , HIV Infections/blood , HIV-1/genetics , Humans , Immunoglobulins, Intravenous/administration & dosage , Immunoglobulins, Intravenous/adverse effects , Infant, Newborn , Infectious Disease Transmission, Vertical , Pregnancy , RNA, Viral/analysis , RNA, Viral/bloodABSTRACT
An intravenous solution of 99% pure globulin (hyperimmune IgG, HIVIG) was obtained from pooled plasma of selected human immunodeficiency virus (HIV-1)-seropositive asymptomatic donors with greater than 400 CD4+/microliters cells per microliter and a high titer of antibody to HIV-1 p24 protein. HIVIG had high titers of antibody to p24, glycoprotein 41 (gp41), and gp120, group-specific neutralizing activity, and binding to the gp120 hypervariable loop region. It inhibited syncytia formation. At low concentration, it enhanced viral production of HIV-1 in infected peripheral blood monocytes but was inhibitory at higher concentration. HIVIG directed group-specific antibody-dependent cellular cytotoxicity against HIV-infected targets. For a period of 6 to 28 months, plasma donors kept stable antibody titers and had a 1.0% decrease in CD4+ cells per month. One gram per kilogram HIVIG injected in two juvenile chimpanzees was well tolerated and did not transmit HIV, as measured by negative cell culture, IgM immune response to HIV proteins, and polymerase chain reaction. The mean half-life of HIV-1 p24 antibody was 15 days. These preliminary data suggest that HIVIG is a safe product suitable for clinical trial in HIV-1-infected individuals.
Subject(s)
HIV Antibodies/isolation & purification , HIV Seropositivity/immunology , HIV/immunology , Immunoglobulins, Intravenous/isolation & purification , Animals , Antibody-Dependent Cell Cytotoxicity , Cytopathogenic Effect, Viral , HIV Antibodies/administration & dosage , HIV Antigens/analysis , Humans , Immunization, Passive , Immunoglobulin Isotypes/immunology , Immunoglobulins, Intravenous/administration & dosage , Injections, Intravenous , Neutralization Tests , Pan troglodytes , Plasmapheresis , T-Lymphocytes/immunologyABSTRACT
Recent studies have demonstrated that commercial preparations of hepatitis B immune globulin often contain antibody to the human immunodeficiency virus. The presence of this antibody has aroused concerns that treatment with hepatitis B immune globulin might passively induce human immunodeficiency virus antibody seropositivity, leading to incorrect diagnoses of human immunodeficiency virus exposure. We studied a group of 16 normal volunteers who received an intramuscular dose of hepatitis B immune globulin (0.06 ml per kg) which was later discovered to contain human immunodeficiency virus antibody. None of the subjects had human immunodeficiency virus antibody before receiving hepatitis B immune globulin. Serum specimens collected at 1 to 4, 6, 8, 12, 16, 20 and 24 weeks after the injection were consistently negative for human immunodeficiency virus antibody. There was no detectable human immunodeficiency virus antibody in any specimen from any subject. We conclude that intramuscular therapy with hepatitis B immune globulin in the recommended dose does not appear to place patients at risk of passive seroconversion to human immunodeficiency virus antibody positivity, despite the presence of antibody in the injected material.
Subject(s)
Antibodies, Viral/administration & dosage , HIV Seropositivity/diagnosis , HIV/immunology , Immunization, Passive , Immunoglobulins/administration & dosage , Adult , Antibodies, Viral/analysis , Female , HIV Seropositivity/immunology , Humans , Immunoglobulins/adverse effects , Immunoglobulins/analysis , Male , Time FactorsABSTRACT
The use of a pepsin solution to digest serum proteins results in quantitative release of thyroxine from carrier proteins. This extraction method greatly simplifies the original Murphy and Pattee (1) competitive protein-binding assay for serum thyroxine. The simplicity and efficiency of this extractant suggest that it may have application in radioimmunoassay and competitive protein-binding assay for nonpeptide ligands in serum.
