A fusion protein of HCMV IE1 exon4 and IE2 exon5 stimulates potent cellular immunity in an MVA vaccine vector.
A therapeutic CMV vaccine incorporating an antigenic repertoire capable of eliciting a cellular immune response has yet to be successfully implemented for patients who already have acquired an infection. To address this problem, we have developed a vaccine candidate derived from modified vaccinia Ankara (MVA) that expresses three immunodominant antigens (pp65, IE1, IE2) from CMV. The novelty of this vaccine is the fusion of two adjacent exons from the immediate-early region of CMV, their successful expression in MVA, and robust immunogenicity in both primary and memory response models. Evaluation of the immunogenicity of the viral vaccine in mouse models shows that it can stimulate primary immunity against all three antigens in both the CD4(+) and CD8(+) T cell subsets. Evaluation of human PBMC from healthy CMV-positive donors or patients within 6 months of receiving hematopoietic cell transplant shows robust stimulation of existing CMV-specific CD4(+) and CD8(+) T cell subsets.
Laboratory of Vaccine Research, Division of Virology, Beckman Research Institute of the City of Hope, California 91010, USA.
Z
Z
Wang
W
W
Zhou
T
T
Srivastava
C
C
La Rosa
A
A
Mandarino
S J
SJ
Forman
J A
JA
Zaia
W J
WJ
Britt
D J
DJ
Diamond
D000818:Animals; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D022482:Cytomegalovirus Vaccines / Q000235:genetics / Q000276:immunology*; D005091:Exons / Q000502:physiology*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D014615:Vaccinia / Q000235:genetics / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000494:pharmacology*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism
D022482:Cytomegalovirus Vaccines; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D010750:Phosphoproteins; D014760:Viral Fusion Proteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa