Safety and immunogenicity of HCV E1E2 vaccine adjuvanted with MF59 administered to healthy adults.
BACKGROUND
Hepatitis C virus (HCV) causes chronic liver disease that often leads to cirrhosis and hepatocellular carcinoma. In animal studies, chimpanzees were protected against chronic infection following experimental challenge with either homologous or heterologous HCV genotype 1a strains which predominate in the USA and Canada. We describe the first in humans clinical trial of this prophylactic HCV vaccine.


METHODS
HCV E1E2 adjuvanted with MF59C.1 (an oil-in-water emulsion) was given at 3 different dosages on day 0 and weeks 4, 24 and 48 in a phase 1, placebo-controlled, dose escalation trial to healthy HCV-negative adults.


RESULTS
There was no significant difference in the proportion of subjects reporting adverse events across the groups. Following vaccination subjects developed antibodies detectable by ELISA, CD81 neutralization and VSV/HCV pseudotype neutralization. There were no significant differences between vaccine groups in the number of responders and geometric mean titers for each of the three assays. All subjects developed lymphocyte proliferation responses to E1E2 and an inverse response to increasing amounts of antigen was noted.


CONCLUSIONS
The vaccine was safe and generally well-tolerated at each of the 3 dosage levels and induced antibody and lymphoproliferative responses. A larger study to further evaluate safety and immunogenicity is warranted.
Frey
Sharon E
SE
Saint Louis University School of Medicine, Division of Infectious Diseases and Immunology, St. Louis, MO 63104, USA. freyse@slu.edu
Houghton
Michael
M
Coates
Stephen
S
Abrignani
Sergio
S
Chien
David
D
Rosa
Domenico
D
Pileri
Piero
P
Ray
Ranjit
R
Di Bisceglie
Adrian M
AM
Rinella
Paola
P
Hill
Heather
H
Wolff
Mark C
MC
Schultze
Viola
V
Han
Jang H
JH
Scharschmidt
Bruce
B
Belshe
Robert B
RB
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D004311:Double-Blind Method; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006508:Hepatitis Antibodies / Q000097:blood; D006526:Hepatitis C / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007115:Immunization Schedule; D008297:Male; D008875:Middle Aged; D011136:Polysorbates / Q000008:administration & dosage*; D013185:Squalene / Q000008:administration & dosage*; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D055815:Young Adult
D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D006508:Hepatitis Antibodies; C089950:MF59 oil emulsion; D011136:Polysorbates; D014761:Viral Hepatitis Vaccines; D013185:Squalene