Andrew D Redd1,2, Nicole A Doria-Rose3, Joshua A Weiner4, Martha Nason5, Matthew Seivers2, Stephen D Schmidt3, Oliver Laeyendecker1,2, Craig Martens6, Daniel Bruno6, Brandon F Keele7, Nagarajan Raju8,9,10, Ivelin S Georgiev8,9,10, Susanna L Lamers11, Jacquie Astemborski12, Gregory D Kirk12, John R Mascola3, Margaret E Ackerman4, Shruti H Mehta12, Thomas C Quinn1,2. 1. Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. 2. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 3. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. 4. Dartmouth College, Hanover, New Hampshire, USA. 5. Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. 6. Genomics Unit, Research Technologies Branch, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA. 7. AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Fredrick, Maryland, USA. 8. Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA. 9. Department of Electrical Engineering and Computer Science, Vanderbilt University, Nashville, Tennessee, USA. 10. Vanderbilt Vaccine Center, Nashville, Tennessee, USA. 11. BioInfoExperts, Thibodaux, Louisiana, USA. 12. Department of Epidemiology, Bloomberg of School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
Abstract
BACKGROUND: Multiple factors influence the human immunodeficiency virus (HIV) antibody response produced during natural infection, leading to responses that can vary in specificity, strength, and breadth. METHODS: People who inject drugs identified as recently infected with HIV (n = 23) were analyzed for clustering of their viral sequences (genetic distance, <2%). Longitudinal antibody responses were identified for neutralizing antibody (Nab) potential, and differences in antibody subclass, specificity, and Fc receptor ligation using pseudovirus entry and multiplexed Fc array assays, respectively. Responses were analyzed for differences between subject groups, defined by similarity in the sequence of the infecting virus. RESULTS: Viral sequences from infected individuals were grouped into 3 distinct clusters with 7 unclustered individuals. Subjects in cluster 1 generally had lower antibody response magnitudes, except for antibodies targeting the V1/V2 region. Subjects in clusters 2 and 3 typically had higher antibody response magnitudes, with the Fv specificity of cluster 2 favoring gp140 recognition. NAb responses differed significantly between clusters for 3 of 18 pseudoviruses examined (P < .05), but there were no differences in overall NAb breadth (P = .62). DISCUSSION: These data demonstrate that individuals infected with similar viral strains can generate partially similar antibody responses, but these do not drastically differ from those in individuals infected with relatively unrelated strains. Published by Oxford University Press for the Infectious Diseases Society of America 2019.
BACKGROUND: Multiple factors influence the human immunodeficiency virus (HIV) antibody response produced during natural infection, leading to responses that can vary in specificity, strength, and breadth. METHODS: People who inject drugs identified as recently infected with HIV (n = 23) were analyzed for clustering of their viral sequences (genetic distance, <2%). Longitudinal antibody responses were identified for neutralizing antibody (Nab) potential, and differences in antibody subclass, specificity, and Fc receptor ligation using pseudovirus entry and multiplexed Fc array assays, respectively. Responses were analyzed for differences between subject groups, defined by similarity in the sequence of the infecting virus. RESULTS: Viral sequences from infected individuals were grouped into 3 distinct clusters with 7 unclustered individuals. Subjects in cluster 1 generally had lower antibody response magnitudes, except for antibodies targeting the V1/V2 region. Subjects in clusters 2 and 3 typically had higher antibody response magnitudes, with the Fv specificity of cluster 2 favoring gp140 recognition. NAb responses differed significantly between clusters for 3 of 18 pseudoviruses examined (P < .05), but there were no differences in overall NAb breadth (P = .62). DISCUSSION: These data demonstrate that individuals infected with similar viral strains can generate partially similar antibody responses, but these do not drastically differ from those in individuals infected with relatively unrelated strains. Published by Oxford University Press for the Infectious Diseases Society of America 2019.
Entities:
Keywords:
HIV; antibody development; cluster linkage; neutralizing antibody; people who inject drugs
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