Primary immune responses are negatively impacted by persistent herpesvirus infections in older people: results from an observational study on healthy subjects and a vaccination trial on subjects aged more than 70 years old

Francesco Nicoli; Emmanuel Clave; Kerstin Wanke; Amrei von Braun; Vincent Bondet; Cécile Alanio; Corinne Douay; Margaux Baque; Claire Lependu; Peggy Marconi; Karin Stiasny; Franz X Heinz; Margot Muetsch; Darragh Duffy; Jacques Boddaert; Delphine Sauce; Antoine Toubert; Urs Karrer; Victor Appay

doi:10.1016/j.ebiom.2022.103852

Primary immune responses are negatively impacted by persistent herpesvirus infections in older people: results from an observational study on healthy subjects and a vaccination trial on subjects aged more than 70 years old

EBioMedicine. 2022 Feb:76:103852. doi: 10.1016/j.ebiom.2022.103852. Epub 2022 Feb 1.

Authors

Francesco Nicoli¹, Emmanuel Clave², Kerstin Wanke³, Amrei von Braun⁴, Vincent Bondet⁵, Cécile Alanio⁶, Corinne Douay², Margaux Baque⁷, Claire Lependu⁷, Peggy Marconi⁸, Karin Stiasny⁹, Franz X Heinz⁹, Margot Muetsch⁴, Darragh Duffy⁵, Jacques Boddaert⁷, Delphine Sauce⁷, Antoine Toubert¹⁰, Urs Karrer¹¹, Victor Appay¹²

Affiliations

¹ Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, INSERM U1135, 75013 Paris, France; Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Ferrara 44121, Italy.
² Université de Paris, Institut de Recherche Saint Louis, EMiLy, Inserm U1160, Paris F-75010, France.
³ Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, Zurich, Switzerland.
⁴ Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich, Zurich, Switzerland.
⁵ Translational Immunology Lab, Institut Pasteur, Université de Paris, Paris, France.
⁶ INSERM U932, PSL University, Institut Curie, Paris 75005, France; Laboratoire D'immunologie Clinique, Institut Curie, Paris 75005, France.
⁷ Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, INSERM U1135, 75013 Paris, France.
⁸ Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Ferrara 44121, Italy.
⁹ Center for Virology, Medical University of Vienna, Austria.
¹⁰ Université de Paris, Institut de Recherche Saint Louis, EMiLy, Inserm U1160, Paris F-75010, France; Laboratoire d'Immunologie et d'Histocompatibilité, AP-HP, Hopital Saint-Louis, Paris F-75010, France.
¹¹ Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, Zurich, Switzerland; Division of Infectious Diseases, Department of Medicine, Cantonal Hospital of Winterthur, Winterthur, Switzerland. Electronic address: urs.karrer@ksw.ch.
¹² Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, INSERM U1135, 75013 Paris, France; Université de Bordeaux, CNRS UMR5164, INSERM ERL1303, ImmunoConcEpT, Bordeaux, France; International Research Center of Medical Sciences, Kumamoto University, Kumamoto, Japan. Electronic address: victor.appay@immuconcept.org.

Abstract

Background: Advanced age is accompanied by a decline of immune functions, which may play a role in increased vulnerability to emerging pathogens and low efficacy of primary vaccinations in elderly people. The capacity to mount immune responses against new antigens is particularly affected in this population. However, its precise determinants are not fully understood. We aimed here at establishing the influence of persistent viral infections on the naive T-cell compartment and primary immune responsiveness in older adults.

Methods: We assessed immunological parameters, related to CD8⁺ and CD4⁺ T-cell responsiveness, according to the serological status for common latent herpesviruses in two independent cohorts: 1) healthy individuals aged 19y to 95y (n = 150) and 2) individuals above 70y old enrolled in a primo-vaccination clinical trial (n = 137).

Findings: We demonstrate a prevalent effect of age and CMV infection on CD8⁺ and CD4⁺ naive T cells, respectively. CMV seropositivity was associated with blunted CD4⁺ T-cell and antibody responses to primary vaccination.

Interpretation: These data provide insights on the changes in adaptive immunity over time and the associated decline in vaccine efficacy with ageing. This knowledge is important for the management of emerging infectious diseases in elderly populations.

Funding: This work was supported by the ANR (Project ANR-14-CE14-0030-01) and by Universita ItaloFrancese/Univeriste FrancoItalienne (Galileo Project G10-718; PHC Galilee Project 39582TJ), by the Swiss National Science Foundation (grant PP0033-110737 to UK), by the Heuberg Foundation (Zurich, Switzerland), by the AETAS Foundation (Geneva, Switzerland) and by a Senior IdEx Chair of the University of Bordeaux (France). EC, VB, CA, MA, DD and AT were supported by the French Government's Investissement d'Avenir Program, Laboratoire d'Excellence "Milieu Interieur" Grant ANR-10-LABX-69-01. EC and AT are supported by the Agence Nationale de la Recherche (Project RANKLthym ANR-19- CE18-0021-02).

Keywords: Elderly; Naive T lymphocytes; T-cell responses; Thymus; Vaccines.

Publication types

Observational Study

MeSH terms

Adult
Aged
Antibody Formation
Cytomegalovirus Infections*
Healthy Volunteers
Herpesviridae*
Humans
Vaccination
Young Adult