title: Influence of frequent infectious exposures on general and varicella-zoster virus-specific immune responses in pediatricians.
abstract: Reexposure to viruses is assumed to strengthen humoral and cellular immunity via the secondary immune response. We studied the effects of frequent exposure to viral infectious challenges on immunity. Furthermore, we assessed whether repetitive exposures to varicella-zoster virus (VZV) elicited persistently high immune responses. Blood samples from 11 pediatricians and matched controls were assessed at 3 time points and 1 time point, respectively. Besides the assessment of general immunity by means of measuring T-cell subset percentages, antibody titers and gamma interferon (IFN-γ)/interleukin 2 (IL-2)-producing T-cell percentages against adenovirus type 5 (AdV-5), cytomegalovirus (CMV), tetanus toxin (TT), and VZV were determined. Pediatricians had lower levels of circulating CD4(+)-naive T cells and showed boosting of CD8(+) effector memory T cells. Although no effect on humoral immunity was seen, repetitive exposures to VZV induced persistently higher percentages of IFN-γ-positive T cells against all VZV antigens tested (VZV glycoprotein E [gE], VZV intermediate-early protein 62 [IE62], and VZV IE63) than in controls. T cells directed against latency-associated VZV IE63 benefitted the most from natural exogenous boosting. Although no differences in cellular or humoral immunity were found between the pediatricians and controls for AdV-5 or TT, we did find larger immune responses against CMV antigens in pediatricians. Despite the high infectious burden, we detected a robust and diverse immune system in pediatricians. Repetitive exposures to VZV have been shown to induce a stable increased level of VZV-specific cellular but not humoral immunity. Based on our observations, VZV IE63 can be considered a candidate for a zoster vaccine.
authors.affiliation: Centre for Health Economics Research and Modeling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.
authors.forename: Benson
authors.initials: B
authors.lastname: Ogunjimi
authors.forename: Evelien
authors.initials: E
authors.lastname: Smits
authors.forename: Steven
authors.initials: S
authors.lastname: Heynderickx
authors.forename: Johan
authors.initials: J
authors.lastname: Van den Bergh
authors.forename: Joke
authors.initials: J
authors.lastname: Bilcke
authors.forename: Hilde
authors.initials: H
authors.lastname: Jansens
authors.forename: Ronald
authors.initials: R
authors.lastname: Malfait
authors.forename: Jose
authors.initials: J
authors.lastname: Ramet
authors.forename: Holden T
authors.initials: HT
authors.lastname: Maecker
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cools
authors.forename: Philippe
authors.initials: P
authors.lastname: Beutels
authors.forename: Pierre
authors.initials: P
authors.lastname: Van Damme
mesh_terms: D000260:Adenoviruses, Human / Q000276:immunology; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D016207:Cytokines / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology; D005260:Female; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D010820:Physicians; D013601:T-Lymphocytes / Q000276:immunology*; D013744:Tetanus Toxin / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D016207:Cytokines; D013744:Tetanus Toxin