Clinical evaluation of safety and immunogenicity of PADRE-cytomegalovirus (CMV) and tetanus-CMV fusion peptide vaccines with or without PF03512676 adjuvant
C La Rosa, J Longmate, SF Lacey… - Journal of Infectious …, 2012 - academic.oup.com
C La Rosa, J Longmate, SF Lacey, T Kaltcheva, R Sharan, D Marsano, P Kwon, J Drake…
Journal of Infectious Diseases, 2012•academic.oup.comBackground. 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 pp65495-503 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 …
protect hematopoietic cell transplant (HCT) recipients from CMV complications. Two
candidate CMV peptide vaccines composed of the HLA A* 0201 pp65495-503 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 …
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 pp65495-503 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 pp65495-503 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 pp65495-503 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 pp65495-503 T cells in healthy adults support further evaluation of CMV peptide vaccines combined with PF03512676 in the HCT setting.
Clinical Trials Registration. NCT00722839.
Oxford University Press