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
Affiliations
Francesco Nicoli
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
Emmanuel Clave
Université de Paris, Institut de Recherche Saint Louis, EMiLy, Inserm U1160, Paris F-75010, France
Kerstin Wanke
Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, Zurich, Switzerland
Amrei von Braun
Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich, Zurich, Switzerland
Vincent Bondet
Translational Immunology Lab, Institut Pasteur, Université de Paris, Paris, France
Cécile Alanio
INSERM U932, PSL University, Institut Curie, Paris 75005, France; Laboratoire D'immunologie Clinique, Institut Curie, Paris 75005, France
Corinne Douay
Université de Paris, Institut de Recherche Saint Louis, EMiLy, Inserm U1160, Paris F-75010, France
Margaux Baque
Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, INSERM U1135, 75013 Paris, France
Claire Lependu
Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, INSERM U1135, 75013 Paris, France
Peggy Marconi
Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Ferrara 44121, Italy
Karin Stiasny
Center for Virology, Medical University of Vienna, Austria
Franz X. Heinz
Center for Virology, Medical University of Vienna, Austria
Margot Muetsch
Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich, Zurich, Switzerland
Darragh Duffy
Translational Immunology Lab, Institut Pasteur, Université de Paris, Paris, France
Jacques Boddaert
Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, INSERM U1135, 75013 Paris, France
Delphine Sauce
Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, INSERM U1135, 75013 Paris, France
Antoine Toubert
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
Urs Karrer
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; Corresponding author at: Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, Zurich, Switzerland.
Victor Appay
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; Corresponding author at: Université de Bordeaux, CNRS UMR5164, INSERM ERL1303, ImmunoConcEpT, Bordeaux, France
Summary: 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.
