scholarly journals Molecular insights into antibody-mediated protection against the prototypic simian immunodeficiency virus

2021 ◽  
Author(s):  
Fangzhu Zhao ◽  
Zachary T Berndsen ◽  
Nuria Pedreno-Lopez ◽  
Alison Burns ◽  
Joel D Allen ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Neutralizing Antibodies ◽  
Low Dose ◽  
Passive Transfer ◽  
Immunodeficiency Virus ◽  
High Resolution Structure ◽  
Structural Insights ◽  
Shed Light ◽  
Sivmac239 Infection ◽  
Resolution Structure

SIVmac239 infection of macaques is a favored model of human HIV infection. However, the SIVmac239 envelope (Env) trimer structure, glycan occupancy, and the targets and ability of neutralizing antibodies (nAbs) to protect against SIVmac239 remain unknown. Here, we report the isolation of SIVmac239 nAbs that recognize a glycan hole and the V1/V4 loop. A high-resolution structure of a SIVmac239 Env trimer-nAb complex shows many similarities to HIV and SIVcpz Envs, but with distinct V4 features and an extended V1 loop. Moreover, SIVmac239 Env has a higher glycan shield density than HIV Env that may contribute to poor or delayed nAb responses in SIVmac239-infected macaques. Passive transfer of a nAb protects macaques from repeated low dose intraveneous SIVmac239 challenge at serum titers comparable to those described for protection of humans against HIV infection. Our results provide structural insights for vaccine design and shed light on antibody-mediated protection in the SIV model.

scholarly journals Vaccine-Induced Cellular Immune Responses Reduce Plasma Viral Concentrations after Repeated Low-Dose Challenge with Pathogenic Simian Immunodeficiency Virus SIVmac239

2006 ◽  
Vol 80 (12) ◽  
pp. 5875-5885 ◽  
Author(s):  
Nancy A. Wilson ◽  
Jason Reed ◽  
Gnankang S. Napoe ◽  
Shari Piaskowski ◽  
Andy Szymanski ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Replication ◽  
Simian Immunodeficiency Virus ◽  
Neutralizing Antibodies ◽  
Low Dose ◽  
Chronic Phase ◽  
Set Point ◽  
Cellular Immune Responses ◽  
Immunodeficiency Virus ◽  
Cellular Immune

ABSTRACT The goal of an AIDS vaccine regimen designed to induce cellular immune responses should be to reduce the viral set point and preserve memory CD4 lymphocytes. Here we investigated whether vaccine-induced cellular immunity in the absence of any Env-specific antibodies can control viral replication following multiple low-dose challenges with the highly pathogenic SIVmac239 isolate. Eight Mamu-A*01-positive Indian rhesus macaques were vaccinated with simian immunodeficiency virus (SIV) gag, tat, rev, and nef using a DNA prime-adenovirus boost strategy. Peak viremia (P = 0.007) and the chronic phase set point (P = 0.0192) were significantly decreased in the vaccinated cohort, out to 1 year postinfection. Loss of CD4+ memory populations was also ameliorated in vaccinated animals. Interestingly, only one of the eight vaccinees developed Env-specific neutralizing antibodies after infection. The control observed was significantly improved over that observed in animals vaccinated with SIV gag only. Vaccine-induced cellular immune responses can, therefore, exert a measure of control over replication of the AIDS virus in the complete absence of neutralizing antibody and give us hope that a vaccine designed to induce cellular immune responses might control viral replication.

Low-dose high-resolution EM of zeolite materials with slow A scan CCD camera

1992 ◽  
Vol 50 (1) ◽  
pp. 302-303
Author(s):  
M. Pan ◽  
P.A. Crozier
Keyword(s):  
Image Processing ◽  
Electron Beam ◽  
High Resolution ◽  
Low Dose ◽  
Ccd Camera ◽  
Low Noise ◽  
Great Sensitivity ◽  
Recording Device ◽  
High Resolution Structure ◽  
Resolution Structure

Zeolite materials are widely used as an important type of catalyst in oil industry. Their catalytic properties and performance are closely related to their unique structures. Use of high resolution electron microscopy (HREM) to characterize structures of zeolite materials has been limited mainly due to the great sensitivity of the framework structures to electron beam irradiation used in the observation. With the recent development in solid state electronics, a new type of image recording device, known as a charge-coupled-device (CCD), has been made possible. Among many of its superior properties, it has been found that the very low noise level present in a slow scan CCD camera offers the possibility of recording high resolution structure images of zeolite materials with very low electron beam dose. The digital storage of CCD images allows on-line image processing to be performed at the microscope, thus making the recording of low dose electron microscope images more efficient. Image processing was also found to be essential in extracting high resolution structure information contained in the noisy low dose HREM CCD images.

scholarly journals Sustained Delivery of a Broadly Neutralizing Antibody in Nonhuman Primates Confers Long-Term Protection against Simian/Human Immunodeficiency Virus Infection

2015 ◽  
Vol 89 (11) ◽  
pp. 5895-5903 ◽  
Author(s):  
Kevin O. Saunders ◽  
Amarendra Pegu ◽  
Ivelin S. Georgiev ◽  
Ming Zeng ◽  
M. Gordon Joyce ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Neutralizing Antibodies ◽  
Nonhuman Primates ◽  
Human Antibody ◽  
Protective Capacity ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Passive Antibody Transfer

ABSTRACTPathogen-specific neutralizing antibodies protect against many viral infections and can potentially prevent human immunodeficiency virus (HIV) transmission in humans. However, neutralizing antibodies have so far only been shown to protect nonhuman primates (NHP) against lentiviral infection when given shortly before challenge. Thus, the clinical utility and feasibility of passive antibody transfer to confer long-term protection against HIV-1 are still debated. Here, we investigate the potential of a broadly neutralizing HIV-1 antibody to provide long-term protection in a NHP model of HIV-1 infection. A human antibody was simianized to avoid immune rejection and used to sustain therapeutic levels for ∼5 months. Two months after the final antibody administration, animals were completely protected against viral challenge. These findings demonstrate the feasibility and potential of long-term passive antibody for protection against HIV-1 in humans and provide a model to test antibody therapies for other diseases in NHP.IMPORTANCEAntibodies against HIV are potential drugs that may be able to prevent HIV infection in humans. However, the long-term protective capacity of antibodies against HIV has not been assessed. Here, we repetitively administered a macaque version of a human anti-HIV antibody to monkeys, after which the antibody persisted in the blood for >5 months. Moreover, the antibody could be sustained at protective levels for 108 days, conferring protection 52 days after the last dose in a monkey model of HIV infection. Thus, passive antibody transfer can provide durable protection against infection by viruses that cause AIDS in primates.

Neurologic Manifestations of Human Immunodeficiency Virus Infection in Children

PEDIATRICS ◽  
1986 ◽  
Vol 78 (4) ◽  
pp. 678-687
Author(s):  
Leon G. Epstein ◽  
Leroy R. Sharer ◽  
James M. Oleske ◽  
Edward M. Connor ◽  
Jaap Goudsmit ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Neutralizing Antibodies ◽  
Fatal Outcome ◽  
Perinatal Period ◽  
Neurologic Manifestations ◽  
Progressive Encephalopathy ◽  
Immunodeficiency Virus ◽  
Aids Related Complex ◽  
Related Complex

This report describes the neurologic manifestations of 36 children with human immunodeficiency virus (HIV) infection. In this cohort, in 16 of 21 children with acquired immunodeficiency syndrome (AIDS), three of 12 children with AIDS-related complex, and one of three asymptomatic seropositive children, a progressive encephalopathy developed. Neurologic signs were often detected early but tended to worsen coincident with progression of the immunodeficiency. The presence of progressive encephalopathy correlated with the absence of serum neutralizing antibodies to HIV and with a poor, usually fatal, outcome. The incubation period from initial HIV infection in the perinatal period to the onset of progressive encephalopathy varied from 2 months to 5 years. Intrablood-brain barrier synthesis of HIV-specific antibodies was demonstrated in eight of 14 children with AIDS and AIDS-related complex, indicating active brain infection with HIV. In three cases this was unassociated with progressive neurologic signs. Unique neuropathologic findings in children who died with HIV infection further suggest that the progressive encephalopathy is the result of primary and persistent infection of the brain with this retrovirus. These findings broaden the spectrum of HIV infection in children and have important implications for the development of antiviral therapy.

scholarly journals Determination of a Statistically Valid Neutralization Titer in Plasma That Confers Protection against Simian-Human Immunodeficiency Virus Challenge following Passive Transfer of High-Titered Neutralizing Antibodies

2002 ◽  
Vol 76 (5) ◽  
pp. 2123-2130 ◽  
Author(s):  
Yoshiaki Nishimura ◽  
Tatsuhiko Igarashi ◽  
Nancy Haigwood ◽  
Reza Sadjadpour ◽  
Ron J. Plishka ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Lymph Node ◽  
Neutralizing Antibodies ◽  
Mononuclear Cells ◽  
Passive Transfer ◽  
Neutralization Titer ◽  
Peripheral Blood Mononuclear ◽  
Vitro Assay ◽  
Immunodeficiency Virus

ABSTRACT We previously reported that high-titered neutralizing antibodies directed against the human immunodeficiency virus type 1 (HIV-1) envelope can block the establishment of a simian immunodeficiency virus (SIV)/HIV chimeric virus (SHIV) infection in two monkeys following passive transfer (R. Shibata et al., Nat. Med. 5:204-210, 1999). In the present study, increasing amounts of neutralizing immunoglobulin G (IgG) were administered to 15 pig-tailed macaques in order to obtain a statistically valid protective neutralization endpoint titer in plasma. Using an in vitro assay which measures complete neutralization of the challenge SHIV, we correlated the titers of neutralizing antibodies in plasma at the time of virus inoculation (which ranged from 1:3 to 1:123) with the establishment of infection in virus-challenged animals. Ten of 15 monkeys in the present experiment were virus free as a result of neutralizing IgG administration as monitored by DNA PCR (peripheral blood mononuclear cells and lymph node cells), RNA PCR (plasma), virus isolation, and the transfer of lymph node cell suspensions (108 cells) plus 8 ml of whole blood from protected animals to naïve macaques. The titer of neutralizing antibodies in the plasma calculated to protect 99% of virus-challenged monkeys was 1:38.

scholarly journals Envelope-Modified Single-Cycle Simian Immunodeficiency Virus Selectively Enhances Antibody Responses and Partially Protects against Repeated, Low-Dose Vaginal Challenge

2010 ◽  
Vol 84 (20) ◽  
pp. 10748-10764 ◽  
Author(s):  
Michael D. Alpert ◽  
Andrew R. Rahmberg ◽  
William Neidermyer ◽  
Sharon K. Ng ◽  
Angela Carville ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Neutralizing Antibodies ◽  
Low Dose ◽  
Rhesus Macaques ◽  
Antibody Responses ◽  
Viral Gene ◽  
Vaginal Mucosa ◽  
Single Cycle ◽  
Glycosylation Sites ◽  
Immunodeficiency Virus

ABSTRACT Immunization of rhesus macaques with strains of simian immunodeficiency virus (SIV) that are limited to a single cycle of infection elicits T-cell responses to multiple viral gene products and antibodies capable of neutralizing lab-adapted SIV, but not neutralization-resistant primary isolates of SIV. In an effort to improve upon the antibody responses, we immunized rhesus macaques with three strains of single-cycle SIV (scSIV) that express envelope glycoproteins modified to lack structural features thought to interfere with the development of neutralizing antibodies. These envelope-modified strains of scSIV lacked either five potential N-linked glycosylation sites in gp120, three potential N-linked glycosylation sites in gp41, or 100 amino acids in the V1V2 region of gp120. Three doses consisting of a mixture of the three envelope-modified strains of scSIV were administered on weeks 0, 6, and 12, followed by two booster inoculations with vesicular stomatitis virus (VSV) G trans-complemented scSIV on weeks 18 and 24. Although this immunization regimen did not elicit antibodies capable of detectably neutralizing SIVmac239 or SIVmac251UCD, neutralizing antibody titers to the envelope-modified strains were selectively enhanced. Virus-specific antibodies and T cells were observed in the vaginal mucosa. After 20 weeks of repeated, low-dose vaginal challenge with SIVmac251UCD, six of eight immunized animals versus six of six naïve controls became infected. Although immunization did not significantly reduce the likelihood of acquiring immunodeficiency virus infection, statistically significant reductions in peak and set point viral loads were observed in the immunized animals relative to the naïve control animals.

scholarly journals Human Immunodeficiency Virus (HIV)-Positive Sera Obtained Shortly after Seroconversion Neutralize Autologous HIV Type 1 Isolates on Primary Macrophages but Not on Lymphocytes

2000 ◽  
Vol 74 (12) ◽  
pp. 5403-5411 ◽  
Author(s):  
Horst Ruppach ◽  
Peter Nara ◽  
Ina Raudonat ◽  
Ziju Elanjikal ◽  
Helga Rübsamen-Waigmann ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Humoral Immunity ◽  
Neutralizing Antibodies ◽  
Autologous Serum ◽  
Hiv Positive ◽  
Target Cells ◽  
Cell Mediated Immunity ◽  
Serum Samples ◽  
Immunodeficiency Virus

ABSTRACT The aim of this study was to analyze the role of humoral immunity in early human immunodeficiency virus (HIV) infection. As neutralizing activities in HIV-positive sera are rarely detectable earlier than 9 to 12 months after infection using primary lymphocytes as target cells in neutralization assays, humoral immunity is generally thought not to contribute significantly to early virus control in the patients. Besides lymphocytes, cells of the monocyte/macrophage lineage are known to be important target cells for HIV in vivo during the establishment of the infection. Therefore, we studied the neutralization of early primary HIV isolates by autologous serum samples using primary macrophages as target cells in the neutralization assays. We analyzed neutralizing activities against the autologous HIV-1 isolates in 10 patients' sera taken shortly after seroconversion, both on primary macrophages and, for comparison, on lymphocytes. Viruses were isolated and expanded in primary mixed cultures containing macrophages and lymphocytes in order to avoid selection for one particular cell type. All viruses replicated to different degrees in macrophages and lymphocytes; nine had a nonsyncytium-inducing phenotype, and one was syncytium inducing. The detection of neutralizing antibodies in acute primary HIV infection depended on the target cells used. Confirming previous studies, we did not find neutralizing activities on lymphocytes at this early time point. In contrast, neutralizing activities were detectable in the same sera if primary macrophages were used as target cells. Differences in neutralizing activities on macrophages and lymphocytes were not due to different virus variants being present in the different cell systems, as gp120 sequences derived from both cell types were homogeneous. Neutralization activities on macrophages did not correlate with the amount of β-chemokines in the sera. As affinity-purified immunoglobulin G preparations from an early patient serum also exhibited neutralization of the autologous virus isolate on primary macrophages, but not on lymphocytes, neutralization is very likely due to antibodies against viral epitopes necessary for infection of macrophages but not for infection of lymphocytes. Our data suggest that, along with cell-mediated immunity, humoral immunity may contribute to the reduction of primary viremia in the patient. This was further supported by a certain association between neutralizing antibody titers on macrophages and viral load in the patients.

scholarly journals Placental Transfer of Respiratory Syncytial Virus Antibody Among HIV-Exposed, Uninfected Infants

2019 ◽  
Vol 9 (3) ◽  
pp. 349-356
Author(s):  
Sweta M Patel ◽  
Sabelle Jallow ◽  
Sefelani Boiditswe ◽  
Shabir A Madhi ◽  
Kristen A Feemster ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Neutralizing Antibodies ◽  
Placental Transfer ◽  
Immunodeficiency Virus ◽  
Maternal Hiv ◽  
Maternal Hiv Infection ◽  
Syncytial Virus ◽  
Hiv Exposed ◽  
Antibody Levels ◽  
Exposed Uninfected

Abstract Background Maternal human immunodeficiency virus (HIV) infection is associated with lower placental transfer of antibodies specific to several childhood pathogens. Our objective for this study was to evaluate the effect of maternal HIV infection on the placental transfer of respiratory syncytial virus (RSV)-neutralizing antibodies. Methods We conducted a cross-sectional study of mothers and their newborn infants at a tertiary hospital in Gaborone, Botswana, between March 2015 and December 2015. We measured serum RSV antibody levels by using a microneutralization assay. We used multivariable linear regression to evaluate the effect of maternal HIV infection on maternal RSV antibody levels, placental transfer of RSV antibodies, and newborn RSV antibody levels. Results Of 316 mothers, 154 (49%) were infected with HIV. The placental transfer ratios for RSV antibodies to HIV-exposed, uninfected (HEU) and HIV-unexposed, uninfected infants were 1.02 and 1.15, respectively. The geometric mean titer (95% confidence interval) of RSV-neutralizing antibodies was 2657 (2251–3136) among HEU newborns and 2911 (2543–3331) among HIV-unexposed, uninfected newborns. In multivariable analyses, maternal HIV infection was associated with lower placental transfer of RSV antibodies (P = .02) and a lower level of RSV antibodies among newborns (P = .002). Among HEU newborns, higher birth weight (P = .004) and an undetectable maternal antenatal viral load (P = .01) were associated with more effective placental transfer of RSV antibodies. Conclusions Maternal human immunodeficiency virus (HIV) infection is associated with lower mother-to-fetus transfer of serum RSV-neutralizing antibodies. HEU infants should be prioritized for preventive interventions for RSV. Maternal viral suppression through combination antiretroviral therapy has the potential to improve immunity to RSV among HIV-exposed infants.

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