Longitudinal Antibody Responses in People Who Inject Drugs Infected With Similar Human Immunodeficiency Virus Strains

Author:

Redd Andrew D12,Doria-Rose Nicole A3,Weiner Joshua A4,Nason Martha5,Seivers Matthew2,Schmidt Stephen D3,Laeyendecker Oliver12,Martens Craig6,Bruno Daniel6,Keele Brandon F7,Raju Nagarajan8910,Georgiev Ivelin S8910,Lamers Susanna L11,Astemborski Jacquie12,Kirk Gregory D12,Mascola John R3,Ackerman Margaret E4,Mehta Shruti H12,Quinn Thomas C12

Affiliation:

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

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.

Funder

Division of Intramural Research and Vaccine Research Center

National Institute of Allergy and Infectious Diseases

National Institute of General Medical Sciences

National Cancer Institute

National Heart Lung and Blood Institute

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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