Antibody Fab-Fc properties outperform titer in predictive models of SIV vaccine-induced protection.
Animals
Antibodies, Viral
/ immunology
CD4-Positive T-Lymphocytes
/ cytology
Humans
Immunity, Humoral
Immunoglobulin Fragments
/ immunology
Immunoglobulin G
/ immunology
Macaca mulatta
Membrane Glycoproteins
/ immunology
Multivariate Analysis
SAIDS Vaccines
/ immunology
Simian Acquired Immunodeficiency Syndrome
/ prevention & control
Simian Immunodeficiency Virus
/ immunology
Viral Envelope Proteins
/ immunology
HIV
antibody effector function
biomarker identification
protection modeling
systems serology
Journal
Molecular systems biology
ISSN: 1744-4292
Titre abrégé: Mol Syst Biol
Pays: England
ID NLM: 101235389
Informations de publication
Date de publication:
02 05 2019
02 05 2019
Historique:
entrez:
4
5
2019
pubmed:
3
5
2019
medline:
12
5
2020
Statut:
epublish
Résumé
Characterizing the antigen-binding and innate immune-recruiting properties of the humoral response offers the chance to obtain deeper insights into mechanisms of protection than revealed by measuring only overall antibody titer. Here, a high-throughput, multiplexed Fab-Fc Array was employed to profile rhesus macaques vaccinated with a gp120-CD4 fusion protein in combination with different genetically encoded adjuvants, and subsequently subjected to multiple heterologous simian immunodeficiency virus (SIV) challenges. Systems analyses modeling protection and adjuvant differences using Fab-Fc Array measurements revealed a set of correlates yielding strong and robust predictive performance, while models based on measurements of response magnitude alone exhibited significantly inferior performance. At the same time, rendering Fab-Fc measurements mathematically independent of titer had relatively little impact on predictive performance. Similar analyses for a distinct SIV vaccine study also showed that Fab-Fc measurements performed significantly better than titer. These results suggest that predictive modeling with measurements of antibody properties can provide detailed correlates with robust predictive power, suggest directions for vaccine improvement, and potentially enable discovery of mechanistic associations.
Identifiants
pubmed: 31048360
doi: 10.15252/msb.20188747
pmc: PMC6497031
doi:
Substances chimiques
Antibodies, Viral
0
Immunoglobulin Fragments
0
Immunoglobulin G
0
Membrane Glycoproteins
0
SAIDS Vaccines
0
Viral Envelope Proteins
0
gp120 protein, Simian immunodeficiency virus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e8747Subventions
Organisme : NIAID NIH HHS
ID : R44 AI091567
Pays : United States
Organisme : NIAID NIH HHS
ID : R44 AI102702
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI131975
Pays : United States
Organisme : NIAID NIH HHS
ID : R44 AI074334
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI080289
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI120756
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI102660
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201100016C
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI124912
Pays : United States
Informations de copyright
© 2019 The Authors. Published under the terms of the CC BY 4.0 license.
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