Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine.
BACKGROUND
The duration of protection afforded by vaccines represents a critical test of their utility as public health interventions. Some vaccines induce long-term immunity, while others require booster doses. Vaccines that induce long-term protection are usually characterized by the generation of immune memory. Recent trials of a quadrivalent (types 6, 11, 16, 18) human papillomavirus (HPV) vaccine have demonstrated high efficacy through 5 years of follow-up. We evaluated the extent to which the vaccine is able to generate HPV type-specific immune memory.


METHODS
A total of 552, 16-23-year-old women were enrolled in a double-blind, placebo-controlled study. At enrollment, subjects were randomized in a 1:1 ratio to receive three-dose regimens of quadrivalent HPV vaccine or placebo with 3 years' follow-up. A subset of 241 subjects (n=114 in the quadrivalent HPV vaccine group and n=127 in the placebo group) underwent 2 further years of follow-up. All extension subjects received quadrivalent HPV vaccine at month 60 to examine the extent of immune memory in response to the primary vaccination series.


RESULTS
Serum anti-HPV levels declined post-vaccination, but reached a plateau at month 24 that remained stable through month 60. Administration of a challenge dose of vaccine induced a classic anamnestic response, with anti-HPV levels 1 week post-challenge reaching levels observed 1 month following the completion of the three-dose primary series. At 1 month post-challenge, anti-HPV responses were higher than those observed 1-month post-dose 3.


CONCLUSIONS
A three-dose regimen of quadrivalent HPV vaccine induces high efficacy and stable anti-HPV levels for at least 5 years. Vaccination also induces robust immune memory. These findings suggest that the efficacy of this vaccine will be long lasting.
Olsson
Sven-Eric
SE
Karolinska Institute at Danderyds Hospital, SE-182 88 Danderyd, Sweden. sven-eric.olsson@ds.se
Villa
Luisa L
LL
Costa
Ronaldo L R
RL
Petta
Carlos A
CA
Andrade
Rosires P
RP
Malm
Christian
C
Iversen
Ole-Erik
OE
Høye
John
J
Steinwall
Margareta
M
Riis-Johannessen
Grete
G
Andersson-Ellstrom
Agneta
A
Elfgren
Kristina
K
von Krogh
Geo
G
Lehtinen
Matti
M
Paavonen
Jorma
J
Tamms
Gretchen M
GM
Giacoletti
Katherine
K
Lupinacci
Lisa
L
Esser
Mark T
MT
Vuocolo
Scott C
SC
Saah
Alfred J
AJ
Barr
Eliav
E
D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005500:Follow-Up Studies; D052140:Human papillomavirus 11 / Q000276:immunology; D052162:Human papillomavirus 16 / Q000276:immunology; D052161:Human papillomavirus 18 / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D007156:Immunologic Memory / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology* / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D053918:Papillomavirus Vaccines