Epitopes described in "Clinical evaluation of safety and immunogenicity of PADRE-cytomegalovirus (CMV) and tetanus-CMV fusion peptide vaccines with or without PF03512676 adjuvant."

Article Authors:Corinna La Rosa; Jeff Longmate; Simon F Lacey; Teodora Kaltcheva; Rahul Sharan; Denise Marsano; Peter Kwon; Jennifer Drake; Brenda Williams; Sharon Denison; Suenell Broyer; Larry Couture; Ryotaro Nakamura; Sanjeet Dadwal; Morris I Kelsey; Arthur M Krieg; Don J Diamond; John A Zaia
Article Title:Clinical evaluation of safety and immunogenicity of PADRE-cytomegalovirus (CMV) and tetanus-CMV fusion peptide vaccines with or without PF03512676 adjuvant.
Reference Detail
Reference ID:1022954
Abstract:BACKGROUND: It has been reported that cytomegalovirus (CMV) pp65-specific T cells can protect hematopoietic cell transplant (HCT) recipients from CMV complications. Two candidate CMV peptide vaccines composed of the HLA A*0201 pp65(495-503) cytotoxic CD8(+) T-cell epitope fused to 2 different universal T-helper epitopes (either the synthetic Pan DR epitope [PADRE] or a natural Tetanus sequence) were clinically evaluated for safety and ability to elicit pp65 T cells in HLA A*0201 healthy volunteers. METHODS: Escalating doses (0.5, 2.5, 10 mg) of PADRE or Tetanus pp65(495-503) vaccines with (30 adults) or without (28 adults) PF03512676 adjuvant were administered by subcutaneous injection every 3 weeks for a total of 4 injections. RESULTS: No serious adverse events were reported, although vaccines used in combination with PF03512676 had enhanced reactogenicity. Ex vivo responses were detected by flow cytometry exclusively in volunteers who received the vaccine coadministered with PF03512676. In addition, using a sensitive in vitro stimulation system, vaccine-elicited pp65(495-503) T cells were expanded in 30% of volunteers injected solely with the CMV peptides and in all tested subjects receiving the vaccines coinjected with PF03512676. CONCLUSIONS: Acceptable safety profiles and vaccine-driven expansion of pp65(495-503) T cells in healthy adults support further evaluation of CMV peptide vaccines combined with PF03512676 in the HCT setting. CLINICAL TRIALS REGISTRATION: NCT00722839.
Affiliations:Division of Translational Vaccine Research, Beckman Research Institute of the City of Hope, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Reference Type:Literature
PubMed ID:22402037
Journal:J Infect Dis
Journal Volume:205
Article Pages:1294-304
Journal ISSN:0022-1899
Article Chemical List:Adjuvants, Immunologic;Cytomegalovirus Vaccines;Epitopes;Malaria Vaccines;Oligodeoxyribonucleotides;PADRE 45;ProMune;Recombinant Proteins;Tetanus Toxoid;Vaccines, Synthetic
Article MeSH List:Adjuvants, Immunologic(administration & dosage; adverse effects); Adolescent; Adult; Amino Acid Sequence; CD8-Positive T-Lymphocytes(physiology); Cytomegalovirus Infections(prevention & control); Cytomegalovirus Vaccines(administration & dosage; adverse effects; immunology); Dose-Response Relationship, Immunologic; Epitopes; Female; Humans; Malaria Vaccines(immunology); Male; Middle Aged; Oligodeoxyribonucleotides(administration & dosage; adverse effects); Recombinant Proteins(immunology); Tetanus Toxoid(administration & dosage; adverse effects; immunology); Vaccines, Synthetic; Young Adult
Article Comments:ErratumIn(J Infect Dis. 2013 Sep;208(6):1038 Dadwal, Sanjeet [added] )
Curation Last Updated:2015-06-05 03:25:44