Novel mechanism of immunosuppression after measles.
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Adult↗
Biomedical subjects
S E Starr
Publications and source records attributed to S E Starr.
Safety and immunogenicity of a combined live attenuated measles, mumps, rubella, and varicella vaccine (MMR(II)V) in healthy children.
An investigational tetravalent combined measles, mumps, rubella, and varicella vaccine and measles-mumps-rubella and varicella vaccines at separate injection sites given at the same visit were evaluated with respect to safety and cell-mediated and humoral immune responses at 6 weeks and 1 year after vaccination. Varicella seroconversion rates and lymphocyte proliferation responses were 100% for both vaccine groups at 6 weeks and 1 year. However, the antibody titer to varicella was lower in the combined vaccine group at 6 weeks, but there was no statistical difference in cell-mediated immune responses. One-year geometric mean titers were not statistically different. Seroconversion rates for measles, mumps, and rubella were 100% for both vaccine at 6 weeks and 1 year. Long-term follow-up of these immune responses is planned.
Antibodies, Viral↗
Mucosal antibodies to human cytomegalovirus glycoprotein B occur following both natural infection and immunization with human cytomegalovirus vaccines.
Because antibodies against human cytomegalovirus (HCMV) glycoprotein B (gB) neutralize, levels of IgG, secretory IgA (sIgA), and mucosal IgA1 antibodies to HCMV were measured in saliva and nasal washes. Ten seronegative adults lacked these antibodies, but of 10 naturally seropositive adults, 10 had IgG to gB, 5 had sIgA, and 0 had mucosal IgA. Among 12 recipients of a live HCMV vaccine, 8 had IgG to gB, 4 had sIgA, and 2 had mucosal IgA in samples collected 10-20 months after immunization; of 10 recipients of a gB vaccine, 8 had IgG to gB, 7 had sIgA, and 7 had mucosal IgA in samples collected just before or 1 month after a booster. IgG to gB and neutralizing titers in serum correlated with IgG to gB in mucosal samples. IgG to gB was in the saliva of 25 of 26 subjects with serum neutralizing titers > 1:64. Serum neutralizing titers > 1:64, whether induced by vaccine or wild type virus, are associated with mucosal IgG to HCMV.
Adolescent↗
Application of the polymerase chain reaction to the diagnosis and management of neonatal herpes simplex virus disease. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.
Cerebrospinal fluid (CSF) specimens from 77 neonates with herpes simplex virus (HSV) disease were evaluated retrospectively by polymerase chain reaction (PCR). Samples were collected from 202 infants enrolled in a National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group trial that compared vidarabine with acyclovir for the treatment of neonatal HSV infection. HSV DNA was detected in the CSF of 26 (76%) of 34 infants with CNS disease, in 13 (93%) of 14 infants with disseminated infection, and in 7 (24%) of 29 with skin, eye, or mouth (SEM) involvement. One of the 7 PCR-positive SEM patients subsequently developed severe neurologic impairment. Eighteen (95%) of 19 infants with positive CSF PCR results after the completion of 10 days of antiviral therapy experienced significant morbidity or mortality. Application of PCR to neonatal HSV disease may provide additional information on which clinical decisions may be based, although its diagnostic utility outside the research setting is unproven.
Brain↗
Resistance to antivirals.
The ability of viruses to develop resistance to antiviral agents is already a major concern with respect to HIV. This article reviews mechanisms and clinical correlates of antiviral resistance and alternative drugs for treatment of infections due to resistant strains of HIV, herpes simplex virus, cytomegalovirus, varicellazoster virus, and influenza A.
Adult↗
Humoral and cell-mediated immune responses in healthy children after one or two doses of varicella vaccine.
This study compared the immune responses of healthy children to one or two doses of Oka/Merck varicella vaccine. Both cell-mediated and humoral immune responses were significantly stronger 1 year later among children given two doses 3 months apart than among those given a single dose. Long-term follow-up studies are needed to determine whether two doses of vaccine indeed provide more complete and more durable protection than a single dose against breakthrough varicella in healthy children.
Antibodies, Viral↗
Immunity induced by primary human cytomegalovirus infection protects against secondary infection among women of childbearing age.
To determine if immunity to human cytomegalovirus (HCMV) protects women from acquiring HCMV from their children, a blinded, randomized protocol was used to monitor seronegative women who received placebo or Towne vaccine (approximately 500 pfu) and seropositive women. Each group was similar for mean maternal (33 years) and child age (18 months) and duration of viral shedding by the child (15 months). Among 19 placebo recipients, 9 developed primary infection; 8 of 19 vaccines but only 3 of 42 naturally seropositive subjects had evidence of acquiring HCMV from their child. Wild type infection and Towne vaccine induced similar mean lymphoproliferative responses to HCMV antigens, but one dose of Towne vaccine produced mean neutralizing titers 10- to 20-fold lower than those after wild type infection. Thus, a vaccine that induces immune responses equal to those induced by wild type virus may protect healthy women from acquiring HCMV from their children.
Adult↗
Varicella vaccine for healthy children.
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Chickenpox↗
Impaired interleukin 12 production in human immunodeficiency virus-infected patients.
Peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected patients, asymptomatic or with acquired immunodeficiency virus, produced 10-fold less interleukin 12 (IL-12) free heavy chain and fivefold less biologically active IL-12 heterodimer than PBMC from uninfected healthy donors when challenged in vitro with the common human pathogen Staphylococcus aureus. In contrast, PBMC from HIV-infected individuals and uninfected control donors produced similar levels of tumor necrosis factor alpha, IL-1 beta, and IL-10, and PBMC from HIV-infected individuals produced three- to fourfold more IL-6 compared with PBMC from uninfected control donors. The defect in IL-12 production is not due to hyperproduction of IL-10, a cytokine exerting an autocrine-negative feedback on IL-12 production, but was directly related to HIV infection, as suggested by the reduced ability of monocytes infected in vitro with HIV to produce IL-12. IL-12 deficiency may be an important component of the immunodeficiency associated with HIV infection.
Adult↗
Cytofluorographic analysis of effects of interferons on expression of human cytomegalovirus proteins.
The appearance of cytomegalovirus (CMV) proteins in infected fibroblasts was determined by flow cytometry. The sequential production of immediate early (IE), early (E), and late (L) proteins reacting with respective monoclonal antibodies (mAbs) E13, 58/5, and 24/4 was determined in fibroblasts infected with the AD-169 strain of CMV. The percentage of cells expressing CMV proteins and the intensity of fluorescence within cells were determined from day 1 to day 7 post-infection. The effect of interferons (IFNs) alpha, beta, gamma on expression of CMV proteins was analyzed using flow cytometry. IFNs inhibited E and L protein production at days 3 and 6 post-infection in a dose-dependent manner. This inhibitory effect on protein expression was associated with a reduction in release of infectious CMV into culture media. The method described here for detection of CMV proteins using flow cytometry may be useful for basic studies of gene expression and for diagnostic purposes.
Antibodies, Monoclonal↗
Enhancing effect of natural killer cell stimulatory factor (NKSF/interleukin-12) on cell-mediated cytotoxicity against tumor-derived and virus-infected cells.
Natural killer cell stimulatory factor (NKSF) or interleukin-12 (IL-12) is a heterodimeric cytokine with pleiomorphic effects on T and NK cells, including induction of lymphokine production, mitogenesis, and enhancement of spontaneous cytotoxic activity. Similarly to IL-2, NKSF/IL-12 enhances NK cell-mediated cytotoxicity within a few hours and independently from induced proliferation. This effect is independent from other induced cytokines, because it is not prevented by antibodies neutralizing interferon (IFN)-alpha, IFN-beta, IFN-gamma, IL-2 or tumor necrosis factor (TNF)-alpha and, unlike the induction of IFN-gamma production by peripheral blood lymphocytes, it does not require HLA class II-positive accessory cells. Enhanced cytotoxicity is accompanied by morphologic changes in NK cells, including a significant increase in the number of cytoplasmic granules. In addition to the previously described ability to enhance the cytotoxic activity of NK cells against tumor-derived target cells, NKSF/IL-12 is also a potent stimulator of cytotoxicity against virus-infected cells, either fibroblasts acutely infected with herpes viruses or T cell lines chronically infected with human immunodeficiency virus-1. NK cell-mediated antibody-dependent cytotoxicity or anti-CD16 antibody-redirected lysis is not significantly enhanced by NKSF/IL-12. However, the ability of resting peripheral blood T cells to mediate anti-CD3 antibody-redirected lysis is enhanced by 18-h incubation with NKSF/IL-12, indicating that this lymphokine can modulate the cytotoxic capability of both NK and T cells.
Animals↗
Morphological and functional differences between HLA-DR+ peripheral blood dendritic cells and HLA-DR+ IFN-alpha producing cells.
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Blood Cells↗
In-vitro infection of peripheral blood dendritic cells with human immunodeficiency virus-1 causes impairment of accessory functions.
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Blood Cells↗
Mycobacterium avium intracellulare complex infection in HIV-infected children.
OBJECTIVE: To describe the incidence of, and risk factors for, Mycobacterium avium intracellulare complex (MAC) infection in HIV-infected children. SETTING: University-affiliated children's hospital. DESIGN AND METHODS: The medical records of 70 HIV-infected infants and children were reviewed retrospectively. RESULTS: Seven children (10% of the HIV-infected patients; 18% of those with AIDS) developed disseminated MAC (dMAC). An additional seven children had gastrointestinal colonization with MAC. Risk of dMAC was associated with increasing age, decreasing CD4 cell count, and (possibly) long-term steroid therapy. CONCLUSIONS: HIV-infected children are at risk of developing dMAC. Children older than 60 months and those with a CD4 cell count < 100 x 10(6)/l are most at risk.
AIDS-Related Opportunistic Infections↗
CD4-independent infection of human peripheral blood dendritic cells with isolates of human immunodeficiency virus type 1.
Dendritic cells (DC) are members of a distinct family of bone marrow-derived leukocytes. DC are potent accessory cells for a number of T cell-mediated immune responses, including autologous and allogeneic mixed leukocyte reactions, and mitogen- and antigen-stimulated lymphocyte proliferation. In the present study, DC purified from human peripheral blood were inoculated with various strains (IIIB, SF2, WMJ1, SF162, 89.6 and clone HXB2) of human immunodeficiency virus type 1 (HIV-1) displaying different patterns of cellular tropism. Viral replication was demonstrated by detection of p24 antigen (Ag) intracellularly and in culture supernatants, and by Southern and Northern blot analyses for the presence of HIV DNA and RNA, respectively, within infected cells. Cell-free and cell-associated p24 Ag levels rose substantially when DC were inoculated with strains SF162, 89.6 and clone HXB2. In contrast, p24 Ag levels rose only marginally after inoculation of DC with strains IIIB, SF2 and WMJ1. Purified DC did not express detectable membrane CD4, although CD4 mRNA was detected by reverse transcriptase PCR. The presence of anti-CD4 monoclonal antibodies failed to block infection of DC by any of the HIV strains tested, suggesting the existence of a CD4-independent alternative pathway of viral entry. The possibility that DC serve as a reservoir for HIV-1 must be considered.
Adult↗
Modified chickenpox in children immunized with the Oka/Merck varicella vaccine.
Oka/Merck varicella vaccine has been studied in this institution since 1981. Persistence of antibody for 6 to 8 years has been demonstrated; however, cases of chickenpox have been seen in immunized children. The severity of chickenpox in healthy children who have received Oka/Merck varicella vaccine since 1981 is described. All vaccinees who developed chickenpox-like rashes more than 6 weeks postimmunization were examined. Of 2163 vaccinees, 164 were examined, of whom 114 had rashes consistent with chickenpox. When sera were available (46%), antibody studies uniformly confirmed varicella-zoster virus infection. Chickenpox occurred 2 to 96 months (median of 44 months) postimmunization. The range for the number of skin lesions was 1 to 285 (median 18) in seroconverters. Symptoms included itching in 39%, fever in 9%, headaches in 7%, lymphadenopathy in 3%, and malaise in 2%; 54% were asymptomatic, except for the rash. The median time to total healing was 5 days. The median time lost from school was 2 days. Thirteen of the children in whom infections developed had failed to seroconvert after immunization. Their infections were similar in severity to those of children who had seroconverted originally. When varicella was introduced into families as a result of chickenpox in an immunized family member (index case), the rate of secondary chickenpox among immunized siblings was 12.2%. Eleven such secondary cases were similar in severity to the 9 index cases. It is concluded that chickenpox is generally mild in previously immunized children.
Adolescent↗
Natural killer (NK) cell stimulatory factor increases the cytotoxic activity of NK cells from both healthy donors and human immunodeficiency virus-infected patients.
Natural killer cell stimulatory factor (NKSF), or interleukin 12 (IL-12), is a heterodimeric lymphokine produced by B cells that has multiple effects on T and NK cell functions. NKSF at concentrations as low as 0.4 pM enhances the spontaneous cytotoxic activity of peripheral blood lymphocytes (PBL) against a variety of tumor-derived target cell lines and virus-infected target cells. The combined treatment of PBL with NKSF and IL-2 results in a less than additive enhancement of cytotoxicity. NKSF enhances the cytotoxic activity of spontaneously cytotoxic CD16+CD5- NK cells and does not confer cytotoxic activity to CD16-CD5+ T cells. PBL from patients infected with human immunodeficiency virus (HIV) have significantly lower cytotoxic activity against tumor-derived target cells and virus-infected target cells than PBL from control healthy donors. Treatment of PBL from HIV-infected patients with NKSF and/or IL-2 results in an increase of NK cell cytotoxicity against both types of target cells to levels similar to or higher than those of untreated PBL from healthy donors. PBL from HIV-infected patients produce interferon gamma in response to NKSF and/or IL-2, although at levels 5- or 10-fold lower than those produced by PBL from healthy donors. The multiple biological effects of NKSF, its activity at very low molar concentrations, and its ability to synergize with other physiological stimuli suggest that NKSF/IL-12 is a lymphokine likely to have physiological importance and considerable therapeutic potential.
Adult↗
Antibody-dependent cellular cytotoxicity (ADCC) is directed against immunodominant epitopes of the envelope proteins of human immunodeficiency virus 1 (HIV-1).
In this study, epitopes of HIV envelope proteins that are involved in ADCC were identified. Peripheral blood mononuclear cells (PBMC) were obtained from adults with asymptomatic HIV infection or early symptoms of AIDS. These PBMC, which were reported to be "armed" in vivo with HIV-specific antibodies, were used as effector cells in 51Cr release assays. Target cells consisted of CD4 lymphocytes from healthy seronegative donors, coated with the IIIB strain of HIV-1 or with one of seven synthetic peptides. Cytotoxicity was detected against CD4 lymphocytes coated with HIV-1 IIIB or with the peptides env aa 507-518, corresponding to the carboxy-terminus of gp120, and env aa 597-611, corresponding to the region of the cysteine loop of gp41. The magnitude of target cell lysis was directly related to the quantity of peptide used. In contrast, target cells coated with the peptide gag aa 129-135, corresponding to the p17/p24 cleavage region of the gag precursor, were not killed. The same immunodominant regions which were involved in ADCC were recognized in enzyme-linked immunoabsorbent assays (ELISA) by the majority of 107 sera from HIV-infected adults. We conclude that the immunodominant epitopes located at the carboxy-terminus of gp120 and the cysteine loop of gp41 serve as recognition structure for antibodies, capable of mediating ADCC against HIV-infected cells.
Antibody-Dependent Cell Cytotoxicity↗