Comparison of antibody responses to human papillomavirus vaccination as measured by three assays.
BACKGROUND
Different assays, including the competitive Luminex immunoassay (cLIA), secreted alkaline phosphatase neutralization assay (SEAP-NA), and virus-like particle-based ELISA, are commonly used to measure antibody responses after human papillomavirus (HPV) vaccination. Direct assay comparisons aid interpretation of immunogenicity data evaluated by different assays.


METHODS
We compared cLIA to SEAP-NA and ELISA among 51 HPV16/18-vaccinated women enrolled in the Costa Rica Vaccine Trial. We tested replicate serum samples collected at months 0, 1, and 12 by HPV16/18 cLIA, SEAP-NA, and ELISA. For a subset (N = 10), we further tested month 6, 24 and 36 samples. We calculated seroprevalence estimates and Spearman rank correlation coefficients comparing cLIA to SEAP-NA and ELISA.


RESULTS
After one vaccine dose, seroprevalence by SEAP-NA and ELISA was 100% (both HPV16 and HPV18), and by cLIA was 96% (95% CI 87-100%) for HPV16 and 71% (95% CI 56-83%) for HPV18. Seroprevalence was 100% by all assays after three doses. Correlation between assays was high after one vaccine dose [cLIA/SEAP-NA ρ = 0.91 (HPV16) and ρ = 0.86 (HPV18); cLIA/ELISA ρ = 0.84 (HPV16) and ρ = 0.74 (HPV18); all p < 0.001] and remained high through month 36. Ratios of mean antibody levels to seropositivity cutoffs at month 36 were lower for cLIA than for SEAP-NA or ELISA, particularly for HPV18 (HPV18 ratio for cLIA 1.9, SEAP-NA 3.5, ELISA 3.4).


CONCLUSIONS
Though correlation between cLIA and SEAP-NA/ELISA is high and stable after vaccination, the assays differ in scale and sensitivity, with notable differences after one vaccine dose and for HPV18. Our results demonstrate that comparisons of antibody responses to HPV vaccination measured by different assays are approximate, and must consider biological and technical differences between assays.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH , Rockville, MD , USA.
Hilary A
HA
Robbins
HPV Immunology Laboratory, SAIC-Frederick Inc., Frederick National Laboratory for Cancer Research , Frederick, MD , USA.
Troy J
TJ
Kemp
Proyecto Epidemiológico Guanacaste, Fundación INCIENSA , Guanacaste , Costa Rica.
Carolina
C
Porras
Proyecto Epidemiológico Guanacaste, Fundación INCIENSA , Guanacaste , Costa Rica.
Ana Cecilia
AC
Rodriguez
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH , Rockville, MD , USA.
Mark
M
Schiffman
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH , Rockville, MD , USA.
Sholom
S
Wacholder
Proyecto Epidemiológico Guanacaste, Fundación INCIENSA , Guanacaste , Costa Rica ; International Agency for Research on Cancer , Lyon , France.
Paula
P
Gonzalez
Center for Cancer Research, National Cancer Institute, NIH , Bethesda, MD , USA.
John
J
Schiller
Center for Cancer Research, National Cancer Institute, NIH , Bethesda, MD , USA.
Douglas
D
Lowy
GlaxoSmithKline Biologicals , Rixensart , Belgium.
Sylviane
S
Poncelet
MedImmune , Gaithersburg, MD , USA.
Mark
M
Esser
PPD Vaccines and Biologics Center of Excellence , Wayne, PA , USA.
Katie
K
Matys
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH , Rockville, MD , USA.
Allan
A
Hildesheim
HPV Immunology Laboratory, SAIC-Frederick Inc., Frederick National Laboratory for Cancer Research , Frederick, MD , USA.
Ligia A
LA
Pinto
Proyecto Epidemiológico Guanacaste, Fundación INCIENSA , Guanacaste , Costa Rica ; International Agency for Research on Cancer , Lyon , France.
Rolando
R
Herrero
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH , Rockville, MD , USA.
Mahboobeh
M
Safaeian
ELISA; HPV serology; HPV vaccines; SEAP-NA; cLIA; human papillomavirus