Assuntos
Antivirais , Infecções por Citomegalovirus , Vacinas contra Citomegalovirus , Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Viremia , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/etiologia , Criança , Citomegalovirus/imunologia , Viremia/etiologia , Feminino , Masculino , Antivirais/uso terapêutico , Antivirais/efeitos adversos , Pré-Escolar , Vacinas contra Citomegalovirus/imunologia , Adolescente , Lactente , Imunogenicidade da VacinaRESUMO
Human cytomegalovirus (CMV) is the most common infectious cause of complications post-transplantation, while a CMV vaccine for transplant recipients has yet to be licensed. Triplex, a multiantigen Modified Vaccinia Ankara (MVA)-vectored CMV vaccine candidate based on the immunodominant antigens phosphoprotein 65 (pp65) and immediate-early 1 and 2 (IE1/2), is in an advanced stage of clinical development. However, its limited genetic and expression stability restricts its potential for large-scale production. Using a recently developed fully synthetic MVA (sMVA) platform, we developed a new generation Triplex vaccine candidate, T10-F10, with different sequence modifications for enhanced vaccine stability. T10-F10 demonstrated genetic and expression stability during extensive virus passaging. In addition, we show that T10-F10 confers comparable immunogenicity to the original Triplex vaccine to elicit antigen-specific T cell responses in HLA-transgenic mice. These results demonstrate improvements in translational vaccine properties of an sMVA-based CMV vaccine candidate designed as a therapeutic treatment for transplant recipients.