Human cytomegalovirus (HCMV)-specific T cell but not neutralizing or IgG binding antibody responses to glycoprotein complexes gB, gHgLgO, and pUL128L correlate with protection against high HCMV viral load reactivation in solid-organ transplant recipients

Daniele Lilleri, Paola Zelini, Chiara Fornara, Federica Zavaglio, Teresa Rampino, Laurent Perez, Elisa Gabanti, Giuseppe Gerna

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Immune correlates of protection against human cytomegalovirus (HCMV) infection are still debated. This study aimed to investigate which arm of the immune response plays a major role in protection against HCMV infection in kidney transplant recipients (n=40) and heart transplant recipients (n=12). Overall, patients were divided into 2 groups: one including 37 patients with low viral load (LVL), and the other including 15 patients with high viral load (HVL). All LVL patients resolved the infection spontaneously, whereas HVL patients were all treated with one or more courses of antivirals. In HVL patients, viral DNAemia, which was more than 100 times higher than LVL, appeared and peaked at significantly earlier times, but disappeared much later than in LVL patients. During a 1-year follow-up, all LVL patients had levels of HCMV-specific CD4+ (and CD8+) T cells significantly higher than HVL patients. On the contrary, titers of neutralizing antibodies and enzyme-linked immunosorbent assay-IgG antibodies to gB, gHgLgO, and pentamer gHgLpUL128L were overlapping in the 2 patient groups. In conclusion, while a valid HCMV-specific T-cell response was detected in more than 90% of LVL patients, >90% of HVL patients lacked an adequate T-cell response. Antibody responses did not appear to be associated directly or indirectly with protection.

Original languageEnglish
JournalJournal of Medical Virology
DOIs
Publication statusAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

Viral Load
Cytomegalovirus
Antibody Formation
Glycoproteins
Immunoglobulin G
T-Lymphocytes
Transplants
Cytomegalovirus Infections
Transplant Recipients
Neutralizing Antibodies
Antiviral Agents
Arm
Enzyme-Linked Immunosorbent Assay
Kidney

Keywords

  • Antibody response
  • High viral load (HVL)
  • Human cytomegalovirus (HCMV)
  • Low viral load (LVL)
  • Solid-organ transplant recipients (SOTR)
  • T-cell response

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

@article{0440dcb2183141828e68f7a742b17061,
title = "Human cytomegalovirus (HCMV)-specific T cell but not neutralizing or IgG binding antibody responses to glycoprotein complexes gB, gHgLgO, and pUL128L correlate with protection against high HCMV viral load reactivation in solid-organ transplant recipients",
abstract = "Immune correlates of protection against human cytomegalovirus (HCMV) infection are still debated. This study aimed to investigate which arm of the immune response plays a major role in protection against HCMV infection in kidney transplant recipients (n=40) and heart transplant recipients (n=12). Overall, patients were divided into 2 groups: one including 37 patients with low viral load (LVL), and the other including 15 patients with high viral load (HVL). All LVL patients resolved the infection spontaneously, whereas HVL patients were all treated with one or more courses of antivirals. In HVL patients, viral DNAemia, which was more than 100 times higher than LVL, appeared and peaked at significantly earlier times, but disappeared much later than in LVL patients. During a 1-year follow-up, all LVL patients had levels of HCMV-specific CD4+ (and CD8+) T cells significantly higher than HVL patients. On the contrary, titers of neutralizing antibodies and enzyme-linked immunosorbent assay-IgG antibodies to gB, gHgLgO, and pentamer gHgLpUL128L were overlapping in the 2 patient groups. In conclusion, while a valid HCMV-specific T-cell response was detected in more than 90{\%} of LVL patients, >90{\%} of HVL patients lacked an adequate T-cell response. Antibody responses did not appear to be associated directly or indirectly with protection.",
keywords = "Antibody response, High viral load (HVL), Human cytomegalovirus (HCMV), Low viral load (LVL), Solid-organ transplant recipients (SOTR), T-cell response",
author = "Daniele Lilleri and Paola Zelini and Chiara Fornara and Federica Zavaglio and Teresa Rampino and Laurent Perez and Elisa Gabanti and Giuseppe Gerna",
year = "2018",
month = "1",
day = "1",
doi = "10.1002/jmv.25225",
language = "English",
journal = "Journal of Medical Virology",
issn = "0146-6615",
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TY - JOUR

T1 - Human cytomegalovirus (HCMV)-specific T cell but not neutralizing or IgG binding antibody responses to glycoprotein complexes gB, gHgLgO, and pUL128L correlate with protection against high HCMV viral load reactivation in solid-organ transplant recipients

AU - Lilleri, Daniele

AU - Zelini, Paola

AU - Fornara, Chiara

AU - Zavaglio, Federica

AU - Rampino, Teresa

AU - Perez, Laurent

AU - Gabanti, Elisa

AU - Gerna, Giuseppe

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Immune correlates of protection against human cytomegalovirus (HCMV) infection are still debated. This study aimed to investigate which arm of the immune response plays a major role in protection against HCMV infection in kidney transplant recipients (n=40) and heart transplant recipients (n=12). Overall, patients were divided into 2 groups: one including 37 patients with low viral load (LVL), and the other including 15 patients with high viral load (HVL). All LVL patients resolved the infection spontaneously, whereas HVL patients were all treated with one or more courses of antivirals. In HVL patients, viral DNAemia, which was more than 100 times higher than LVL, appeared and peaked at significantly earlier times, but disappeared much later than in LVL patients. During a 1-year follow-up, all LVL patients had levels of HCMV-specific CD4+ (and CD8+) T cells significantly higher than HVL patients. On the contrary, titers of neutralizing antibodies and enzyme-linked immunosorbent assay-IgG antibodies to gB, gHgLgO, and pentamer gHgLpUL128L were overlapping in the 2 patient groups. In conclusion, while a valid HCMV-specific T-cell response was detected in more than 90% of LVL patients, >90% of HVL patients lacked an adequate T-cell response. Antibody responses did not appear to be associated directly or indirectly with protection.

AB - Immune correlates of protection against human cytomegalovirus (HCMV) infection are still debated. This study aimed to investigate which arm of the immune response plays a major role in protection against HCMV infection in kidney transplant recipients (n=40) and heart transplant recipients (n=12). Overall, patients were divided into 2 groups: one including 37 patients with low viral load (LVL), and the other including 15 patients with high viral load (HVL). All LVL patients resolved the infection spontaneously, whereas HVL patients were all treated with one or more courses of antivirals. In HVL patients, viral DNAemia, which was more than 100 times higher than LVL, appeared and peaked at significantly earlier times, but disappeared much later than in LVL patients. During a 1-year follow-up, all LVL patients had levels of HCMV-specific CD4+ (and CD8+) T cells significantly higher than HVL patients. On the contrary, titers of neutralizing antibodies and enzyme-linked immunosorbent assay-IgG antibodies to gB, gHgLgO, and pentamer gHgLpUL128L were overlapping in the 2 patient groups. In conclusion, while a valid HCMV-specific T-cell response was detected in more than 90% of LVL patients, >90% of HVL patients lacked an adequate T-cell response. Antibody responses did not appear to be associated directly or indirectly with protection.

KW - Antibody response

KW - High viral load (HVL)

KW - Human cytomegalovirus (HCMV)

KW - Low viral load (LVL)

KW - Solid-organ transplant recipients (SOTR)

KW - T-cell response

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