title: The Breadth of Synthetic Long Peptide Vaccine-Induced CD8+ T Cell Responses Determines the Efficacy against Mouse Cytomegalovirus Infection.
abstract: There is an ultimate need for efficacious vaccines against human cytomegalovirus (HCMV), which causes severe morbidity and mortality among neonates and immunocompromised individuals. In this study we explored synthetic long peptide (SLP) vaccination as a platform modality to protect against mouse CMV (MCMV) infection in preclinical mouse models. In both C57BL/6 and BALB/c mouse strains, prime-booster vaccination with SLPs containing MHC class I restricted epitopes of MCMV resulted in the induction of strong and polyfunctional (i.e., IFN-γ+, TNF+, IL-2+) CD8+ T cell responses, equivalent in magnitude to those induced by the virus itself. SLP vaccination initially led to the formation of effector CD8+ T cells (KLRG1hi, CD44hi, CD127lo, CD62Llo), which eventually converted to a mixed central and effector-memory T cell phenotype. Markedly, the magnitude of the SLP vaccine-induced CD8+ T cell response was unrelated to the T cell functional avidity but correlated to the naive CD8+ T cell precursor frequency of each epitope. Vaccination with single SLPs displayed various levels of long-term protection against acute MCMV infection, but superior protection occurred after vaccination with a combination of SLPs. This finding underlines the importance of the breadth of the vaccine-induced CD8+ T cell response. Thus, SLP-based vaccines could be a potential strategy to prevent CMV-associated disease.
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Eleni
authors.initials: E
authors.lastname: Panagioti
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Anke
authors.initials: A
authors.lastname: Redeker
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Suzanne
authors.initials: S
authors.lastname: van Duikeren
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Kees Lmc
authors.initials: KL
authors.lastname: Franken
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jan Wouter
authors.initials: JW
authors.lastname: Drijfhout
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Sjoerd H
authors.initials: SH
authors.lastname: van der Burg
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ramon
authors.identifier: 0000-0001-5058-4110
authors.initials: R
authors.lastname: Arens
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000276:immunology*; D014611:Vaccination; D022223:Vaccines, Subunit / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D016207:Cytokines; D000939:Epitopes; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic