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Characterization of Plasma Immunoglobulin G Responses in Elite Neutralizers of Human Cytomegalovirus.

Publication ,  Journal Article
Harnois, MJ; Dennis, M; Stöhr, D; Valencia, SM; Rodgers, N; Semmes, EC; Webster, HS; Jenks, JA; Barfield, R; Pollara, J; Chan, C; Sinzger, C ...
Published in: J Infect Dis
November 1, 2022

BACKGROUND: Human cytomegalovirus (HCMV) is the most common infectious complication of organ transplantation and cause of birth defects worldwide. There are limited therapeutic options and no licensed vaccine to prevent HCMV infection or disease. To inform development of HCMV antibody-based interventions, a previous study identified individuals with potent and broad plasma HCMV-neutralizing activity, termed elite neutralizers (ENs), from a cohort of HCMV-seropositive (SP) blood donors. However, the specificities and functions of plasma antibodies associated with EN status remained undefined. METHODS: We sought to determine the plasma antibody specificities, breadth, and Fc-mediated antibody effector functions associated with the most potent HCMV-neutralizing responses in plasma from ENs (n = 25) relative to that from SP donors (n = 19). We measured antibody binding against various HCMV strains and glycoprotein targets and evaluated Fc-mediated effector functions, antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP). RESULTS: We demonstrate that ENs have elevated immunoglobulin G binding responses against multiple viral glycoproteins, relative to SP donors. Our study also revealed potent HCMV-specific antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis activity of plasma from ENs. CONCLUSIONS: We conclude that antibody responses against multiple glycoprotein specificities may be needed to achieve potent plasma neutralization and that potently HCMV elite-neutralizing plasma antibodies can also mediate polyfunctional responses.

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Published In

J Infect Dis

DOI

EISSN

1537-6613

Publication Date

November 1, 2022

Volume

226

Issue

9

Start / End Page

1667 / 1677

Location

United States

Related Subject Headings

  • Viral Envelope Proteins
  • Microbiology
  • Immunoglobulin G
  • Humans
  • Cytomegalovirus Infections
  • Cytomegalovirus
  • Antibody Formation
  • Antibodies, Viral
  • Antibodies, Neutralizing
  • 42 Health sciences
 

Citation

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Harnois, M. J., Dennis, M., Stöhr, D., Valencia, S. M., Rodgers, N., Semmes, E. C., … Permar, S. R. (2022). Characterization of Plasma Immunoglobulin G Responses in Elite Neutralizers of Human Cytomegalovirus. J Infect Dis, 226(9), 1667–1677. https://doi.org/10.1093/infdis/jiac341
Harnois, Melissa J., Maria Dennis, Dagmar Stöhr, Sarah M. Valencia, Nicole Rodgers, Eleanor C. Semmes, Helen S. Webster, et al. “Characterization of Plasma Immunoglobulin G Responses in Elite Neutralizers of Human Cytomegalovirus.J Infect Dis 226, no. 9 (November 1, 2022): 1667–77. https://doi.org/10.1093/infdis/jiac341.
Harnois MJ, Dennis M, Stöhr D, Valencia SM, Rodgers N, Semmes EC, et al. Characterization of Plasma Immunoglobulin G Responses in Elite Neutralizers of Human Cytomegalovirus. J Infect Dis. 2022 Nov 1;226(9):1667–77.
Harnois, Melissa J., et al. “Characterization of Plasma Immunoglobulin G Responses in Elite Neutralizers of Human Cytomegalovirus.J Infect Dis, vol. 226, no. 9, Nov. 2022, pp. 1667–77. Pubmed, doi:10.1093/infdis/jiac341.
Harnois MJ, Dennis M, Stöhr D, Valencia SM, Rodgers N, Semmes EC, Webster HS, Jenks JA, Barfield R, Pollara J, Chan C, Sinzger C, Permar SR. Characterization of Plasma Immunoglobulin G Responses in Elite Neutralizers of Human Cytomegalovirus. J Infect Dis. 2022 Nov 1;226(9):1667–1677.
Journal cover image

Published In

J Infect Dis

DOI

EISSN

1537-6613

Publication Date

November 1, 2022

Volume

226

Issue

9

Start / End Page

1667 / 1677

Location

United States

Related Subject Headings

  • Viral Envelope Proteins
  • Microbiology
  • Immunoglobulin G
  • Humans
  • Cytomegalovirus Infections
  • Cytomegalovirus
  • Antibody Formation
  • Antibodies, Viral
  • Antibodies, Neutralizing
  • 42 Health sciences