Persistence of Varicella-Zoster Virus-Specific Plasma Cells in Adult Human Bone Marrow following Childhood Vaccination

• Published in: Journal of virology 2020-06, Vol.94 (13)
• Main Authors: Eberhardt, Christiane S, Wieland, Andreas, Nasti, Tahseen H, Grifoni, Alba, Wilson, Elizabeth, Schmid, D Scott, Pulendran, Bali, Sette, Alessandro, Waller, Edmund K, Rouphael, Nadine, Ahmed, Rafi
• Format: Article
• Language: English
• Subjects: Antibodies, Viral - immunology; Bone Marrow; CD4-Positive T-Lymphocytes - immunology; Female; Herpes Zoster - immunology; Herpes Zoster Vaccine - immunology; Herpesvirus 3, Human - immunology; Humans; Immunity, Cellular - immunology; Interferon-gamma - immunology; Leukocytes, Mononuclear - immunology; Male; Plasma Cells - immunology; Vaccination; Vaccines and Antiviral Agents; Vaccines, Attenuated - immunology; Young Adult
• ISSN: 0022-538X; 1098-5514
• DOI: 10.1128/JVI.02127-19

Childhood immunization with the live-attenuated varicella-zoster virus (VZV) vaccine induces protective immune responses. Routine VZV vaccination started only 2 decades ago, and thus, there are few studies examining the longevity of vaccine-induced immunity. Here, we analyzed the quantity of VZV-specific plasma cells (PCs) and CD4 T cells in the bone marrow (BM) of healthy young adults (  = 15) following childhood VZV immunization. Long-lived BM resident plasma cells constitutively secrete antibodies, and we detected VZV-specific PCs in the BM of all subjects. Anti-VZV plasma antibody titers correlated positively with the number of VZV-specific BM PCs. Furthermore, we quantified the number of interferon gamma (IFN-γ)-producing CD4 T cells specific for VZV glycoprotein E and all other structural and nonstructural VZV proteins in both BM and blood (peripheral blood mononuclear cells [PBMCs]). The frequency of VZV-specific IFN-γ-producing CD4 T cells was significantly higher in PBMCs than BM. Our study shows that VZV-specific PCs and VZV-specific CD4 memory T cells persist up to 20 years after vaccination. These findings indicate that childhood VZV vaccination can elicit long-lived immune memory responses in the bone marrow. Childhood varicella-zoster virus (VZV) immunization induces immune memory responses that protect against primary VZV infection, chicken pox. In the United States, routine childhood VZV vaccination was introduced only 2 decades ago. Hence, there is limited information on the longevity of B and CD4 T cell memory, which are both important for protection. Here, we showed in 15 healthy young adults that VZV-specific B and CD4 T cell responses are detectable in bone marrow (BM) and blood up to 20 years after vaccination. Specifically, we measured antibody-secreting plasma cells in the BM and VZV-specific CD4 T cells in BM and blood. These findings suggest that childhood VZV vaccination induces long-lived immunity.