Neutralizing antibody responses in acute HIV-1 subtype C infection The study of the evolution and specificities of neutralizing antibodies during the course of HIV-1 infection may be important in the discovery of possible targets for vaccine design. In this study we assessed the autologous and heterologous neutralization response in 14 HIV-1 subtype C infected individuals using envelope clones obtained within the first 2 months post-infection. Our data shows that potent, but relatively strain-specific, neutralizing antibodies develop within 3-12 months of HIV-1 infection. The magnitude of this response was associated with shorter envelope length and fewer glycosylation sites particularly in the V1-V2 region. Anti-MPER antibodies were detected in 4 of 14 individuals within a year of infection, while antibodies to CD4-induced epitopes developed to high titer in 12 participants and in most cases before autologous neutralizing antibodies. However, neither anti-MPER nor anti-CD4i antibody specificities conferred neutralization breadth, at least within the first year of infection. These data provide insights into the kinetics, potency, breadth, and epitope specificity of neutralizing antibody responses in acute HIV-1 subtype C infection. Mapping the specificity of broadly neutralizing sera HIV-1 positive plasma samples obtained from the South Africa blood bank were used to determine whether neutralization breadth was associated with anti-CD4i or anti-MPER antibodies. The BED ELISA was performed to exclude samples from donors with recent infection which may confound the analysis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI067854-05
Application #
7896719
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
5
Fiscal Year
2009
Total Cost
$1,795,460
Indirect Cost
Name
Duke University
Department
Type
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Song, Hongshuo; Giorgi, Elena E; Ganusov, Vitaly V et al. (2018) Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection. Nat Commun 9:1928
Boelen, Lies; Debebe, Bisrat; Silveira, Marcos et al. (2018) Inhibitory killer cell immunoglobulin-like receptors strengthen CD8+ T cell-mediated control of HIV-1, HCV, and HTLV-1. Sci Immunol 3:
Winawer, Melodie R; Griffin, Nicole G; Samanamud, Jorge et al. (2018) Somatic SLC35A2 variants in the brain are associated with intractable neocortical epilepsy. Ann Neurol 83:1133-1146
Epi4K Consortium; EuroEPINOMICS-RES Consortium; Epilepsy Phenome Genome Project (2017) Application of rare variant transmission disequilibrium tests to epileptic encephalopathy trio sequence data. Eur J Hum Genet 25:894-899
Liu, Donglai; Wang, Chu; Hora, Bhavna et al. (2017) A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies. Retrovirology 14:46
Pacheco, Beatriz; Alsahafi, Nirmin; Debbeche, Olfa et al. (2017) Residues in the gp41 Ectodomain Regulate HIV-1 Envelope Glycoprotein Conformational Transitions Induced by gp120-Directed Inhibitors. J Virol 91:
Fouda, Genevieve G; Eudailey, Joshua; Kunz, Erika L et al. (2017) Systemic administration of an HIV-1 broadly neutralizing dimeric IgA yields mucosal secretory IgA and virus neutralization. Mucosal Immunol 10:228-237
Shen, Xiaoying; Bogers, Willy M; Yates, Nicole L et al. (2017) Cross-Linking of a CD4-Mimetic Miniprotein with HIV-1 Env gp140 Alters Kinetics and Specificities of Antibody Responses against HIV-1 Env in Macaques. J Virol 91:
Fischetti, Lucia; Zhong, Ziyun; Pinder, Christopher L et al. (2017) The synergistic effects of combining TLR ligand based adjuvants on the cytokine response are dependent upon p38/JNK signalling. Cytokine 99:287-296
Gelfman, Sahar; Wang, Quanli; McSweeney, K Melodi et al. (2017) Annotating pathogenic non-coding variants in genic regions. Nat Commun 8:236

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