Clinical Evaluation of Safety and Immunogenicity of PADRE-cytomegalovirus (CMV) and Tetanus-CMV Fusion Peptide Vaccines with or Without PF03512676 Adjuvant

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2012 Mar 10

PMID 22402037

Citations 45

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

Affiliations

Soon will be listed here.

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.

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