Enhancement of human papillomavirus (HPV) type 16 E6 and E7-specific T-cell immunity in healthy volunteers through vaccination with TA-CIN, an HPV16 L2E7E6 fusion protein vaccine.
TA-CIN is a vaccine that comprises the human papillomavirus (HPV) type 16 L2, E6 and E7 as a single fusion protein. In a mouse model, TA-CIN effectively prevented outgrowth of HPV16-positive tumour cells. To assess the safety and immunogenicity of TA-CIN, a dose escalating (26, 128, 533 micro g), double blind and placebo-controlled phase I study was conducted in 40 healthy volunteers. TA-CIN was administered without adjuvant by intramuscular injection on weeks 0, 4 and 8. No serious adverse events of the vaccination were reported during the study. Both IgG antibodies and proliferative responses against TA-CIN were elicited at all three doses. More importantly, T-cell immunity against the HPV16 E6 and E7 oncoproteins was detected by IFN gamma ELISPOT in 8/11 evaluable subjects vaccinated with the 533 micro g dose.
de Jong
A
A
Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, PO Box 9600, 2300 RC, Leiden, The Netherlands.
O'Neill
T
T
Khan
A Y
AY
Kwappenberg
K M C
KM
Chisholm
S E
SE
Whittle
N R
NR
Dobson
J A
JA
Jack
L C
LC
St Clair Roberts
J A
JA
Offringa
R
R
van der Burg
S H
SH
Hickling
J K
JK
D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D002213:Capsid / Q000276:immunology*; D036022:Capsid Proteins; D005260:Female; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D012097:Repressor Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*; D014765:Viral Vaccines / Q000009:adverse effects / Q000276:immunology*
D000914:Antibodies, Viral; D036022:Capsid Proteins; C068651:E6 protein, Human papillomavirus type 16; D007074:Immunoglobulin G; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D012097:Repressor Proteins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16