Assessment of HPV 16 and HPV 18 antibody responses by pseudovirus neutralization, Merck cLIA and Merck total IgG LIA immunoassays in a reduced dosage quadrivalent HPV vaccine trial.
We assessed HPV 16 and 18 antibody responses of female subjects enrolled in a 2- vs. 3-dose quadrivalent HPV (Q-HPV) vaccine trial (ClinicalTrials.gov NCT00501137) using the Merck competitive Luminex (cLIA) and total IgG Luminex (TIgG) immunoassays, and a pseudovirus neutralizing antibody (PsV NAb) assay. Subjects were enrolled in one of three groups: (1) 9-13yr, 2 doses of Q-HPV at 0, 6 months (n=259); (2) 9-13yr, 3 doses at 0, 2, 6 months (n=260); and (3) 16-26yr, 3 doses at 0, 2, 6 months (n=305). Sera were collected from all subjects at baseline, months 7 and 24, and from half the subjects at months 18 and 36. High correlation was observed between all three assays. At month 36, HPV 16 antibodies remained detectable in all subjects by all assays, whereas 86.4%, 99.6% and 100% of subjects respectively were HPV 18 cLIA, TIgG and PsV NAb (partial neutralization endpoint) seropositive. The proportion seropositive for HPV 18 by cLIA at 36 months was not significantly different for 2-dose girls vs. 3-dose adults (85.9% vs. 79.4%; p=0.51), whereas the proportion for 3-dose girls was significantly higher than for 3-dose adults (95.3% vs. 79.4%; p<0.01). The HPV 18 seropositive proportions by the TIgG and PsV NAb (partial neutralization endpoint) assays were the same for all subjects. High baseline HPV 16 and HPV 18 seropositivity was observed for the TIgG assay and it is unclear if all the detected TIgG antibodies are type-specific and/or neutralizing. For the PsV NAb assay, 90% and partial neutralization geometric mean titres were consistently 2-8-fold higher than for 100% neutralization, which enabled detection of HPV 18 NAb in subjects who lost detectable cLIA antibodies over time. We conclude that the PsV NAb assay is more sensitive than the cLIA, and likely more specific than the TIgG assay.
British Columbia Centre for Disease Control, 655 West 12th Avenue, Vancouver, Canada; Faculty of Medicine, University of British Columbia, 317 - 2194 Health Sciences Mall, Vancouver, Canada. Electronic address: mel.krajden@bccdc.ca.
Mel
M
Krajden
British Columbia Centre for Disease Control, 655 West 12th Avenue, Vancouver, Canada. Electronic address: darrel.cook@bccdc.ca.
Darrel
D
Cook
British Columbia Centre for Disease Control, 655 West 12th Avenue, Vancouver, Canada. Electronic address: amanda.yu@bccdc.ca.
Amanda
A
Yu
Provincial Health Services Authority Laboratories, 655 West 12th Avenue, Vancouver, Canada. Electronic address: ron.chow@bccdc.ca.
Ron
R
Chow
Provincial Health Services Authority Laboratories, 655 West 12th Avenue, Vancouver, Canada. Electronic address: qiang.su@bccdc.ca.
Qiang
Q
Su
Provincial Health Services Authority Laboratories, 655 West 12th Avenue, Vancouver, Canada. Electronic address: wendy.mei@bccdc.ca.
Wendy
W
Mei
Centre for Vaccinology, Dalhousie University, 5850 University Avenue, Halifax, Canada. Electronic address: shelly.mcneil@cdha.nshealth.ca.
Shelly
S
McNeil
Faculty of Medicine, University of British Columbia, 317 - 2194 Health Sciences Mall, Vancouver, Canada. Electronic address: dmoney@cw.bc.ca.
Deborah
D
Money
Centre de recherche du CHUL, Université Laval, 2400 D'Estimauville, Québec, Canada. Electronic address: marc.dionne@inspq.qc.ca.
Marc
M
Dionne
University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143, USA. Electronic address: joel.palefsky@ucsf.edu.
Joel
J
Palefsky
British Columbia Centre for Disease Control, 655 West 12th Avenue, Vancouver, Canada. Electronic address: Karuna.Karunakaran@bccdc.ca.
Karuna
K
Karunakaran
Faculty of Medicine, University of British Columbia, 317 - 2194 Health Sciences Mall, Vancouver, Canada; Vaccine Evaluation Centre, BC Children's Hospital, 950 West 28th Avenue, Vancouver, Canada. Electronic address: tKollmann@cw.bc.ca.
Tobias
T
Kollmann
British Columbia Centre for Disease Control, 655 West 12th Avenue, Vancouver, Canada; Faculty of Medicine, University of British Columbia, 317 - 2194 Health Sciences Mall, Vancouver, Canada. Electronic address: gina.ogilvie@bccdc.ca.
Gina
G
Ogilvie
British Columbia Centre for Disease Control, 655 West 12th Avenue, Vancouver, Canada; Faculty of Medicine, University of British Columbia, 317 - 2194 Health Sciences Mall, Vancouver, Canada. Electronic address: martin.petric@bccdc.ca.
Martin
M
Petric
Faculty of Medicine, University of British Columbia, 317 - 2194 Health Sciences Mall, Vancouver, Canada; Vaccine Evaluation Centre, BC Children's Hospital, 950 West 28th Avenue, Vancouver, Canada. Electronic address: sdobson@cw.bc.ca.
Simon
S
Dobson
D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D005260:Female; D052162:Human papillomavirus 16; D052161:Human papillomavirus 18; D006801:Humans; D007115:Immunization Schedule; D007118:Immunoassay / Q000379:methods*; D009500:Neutralization Tests; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000008:administration & dosage*; D012680:Sensitivity and Specificity; D055815:Young Adult
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D053918:Papillomavirus Vaccines
100% neutralization endpoint; 90% neutralization endpoint; Antibody response; EIA; GMT; HPV vaccine; Merck cLIA; Merck competitive Luminex immunoassay; Merck total IgG LIA; Merck total IgG Luminex immunoassay; NT(100); NT(90); NT(partial); PsV NAb; Pseudovirus neutralization; Q-HPV; RFP; TIgG; VLP; cLIA; enzyme immunoassay; geometric mean titre; mMU; milli-Merck units; partial neutralization endpoint; pseudovirus neutralizing antibody; quadrivalent HPV; red fluorescent protein; virus-like particle