The long-term immune response after HPV16 peptide vaccination in women with low-grade pre-malignant disorders of the uterine cervix: a placebo-controlled phase II study.
The capacity of a low-dose HPV16 synthetic long-peptide vaccine (HPV16-SLP) to induce an HPV16-specific T-cell response as well as to establish long-term immunologic memory in patients with low-grade abnormalities of the cervix was determined in a placebo-controlled, double-blinded phase II study. In addition, the effect of a booster vaccination after 1 year was evaluated. Patients received either the HPV16-SLP or a placebo at the start of the study. After 1 year, the vaccinated patients were again randomized to receive the HPV16-SLP or a placebo. Patients were followed for 2 years. HPV16-specific T-cell responses were determined in pre- and post-vaccination blood samples by ELISPOT, proliferation assay and cytokine assays. We show that the HPV16-specific T-cell responses detected after vaccination are clearly due to vaccination and that reactivity was maintained for at least 2 years. Interestingly, a booster vaccination after 1 year especially augmented the HPV16-specific Th2 response. Furthermore, pre-existing immunity to HPV16 was associated with a stronger response to vaccination and with more side effects, reflected by flu-like symptoms. We conclude that two low-dose injections of HPV16-SLP can induce a strong and stable HPV16-specific T-cell response that lasts for at least 1 year. If booster vaccination is required, then polarizing adjuvant should be added to maintain the Th1 focus of the vaccine-induced T-cell response.
Peggy J
PJ
de Vos van Steenwijk
Mariette I E
MI
van Poelgeest
Tamara H
TH
Ramwadhdoebe
Margriet J G
MJ
Löwik
Dorien M A
DM
Berends-van der Meer
Caroline E
CE
van der Minne
Nikki M
NM
Loof
Linda F M
LF
Stynenbosch
Lorraine M
LM
Fathers
A Rob P M
AR
Valentijn
Jaap
J
Oostendorp
Elisabeth M
EM
Osse
Gert Jan
GJ
Fleuren
Linda
L
Nooij
Marjolein J
MJ
Kagie
Bart W J
BW
Hellebrekers
Cornelis J M
CJ
Melief
Marij J P
MJ
Welters
Sjoerd H
SH
van der Burg
Gemma G
GG
Kenter
D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008875:Middle Aged; D060787:Neoplasm Grading; D053918:Papillomavirus Vaccines / Q000276:immunology*; D011230:Precancerous Conditions / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology / Q000821:virology; D014611:Vaccination / Q000009:adverse effects; D022223:Vaccines, Subunit / Q000276:immunology
D053918:Papillomavirus Vaccines; D022223:Vaccines, Subunit