Characterization of the HPV-specific memory B cell and systemic antibody responses in women receiving an unadjuvanted HPV16 L1 VLP vaccine

Abstract

Human papillomavirus (HPV)-specific antibodies are proposed to be the correlate of protection afforded by HPV L1 virus-like particle (VLP) vaccines. Previous studies have characterized the systemic antibody response to immunization in terms of both the quantity and the ability to neutralize HPV. Here, we have adapted a generalized memory B cell ELISPOT to the HPV16 system and expanded the analysis of the systemic antibody response to include an avidity measurement of HPV L1 VLP-specific antibodies. We show the results of the memory B cell ELISPOT significantly correlated with IgG and neutralizing antibody titers, but not with the avidity measurement. This is the first comprehensive study to correlate a variety of humoral aspects potentially associated with protective immunity following vaccination with a HPV16 L1 VLP vaccine.

Copyright 2010 Elsevier Ltd. All rights reserved.

Figures

Fig. 1

Summary of the HPV16-specific IgG memory B cell response kinetics. Participants were vaccinated with an unadjuvanted, HPV16 L1 VLP vaccine at months 0, 1, and 6. HPV16-specific memory B cells secreting IgG after polyclonal stimulation were tracked at months 0, 2, and 7. The open circles represent each individual with a positive memory B cell response. The values in parentheses are the number of positives within the total number of individuals tested. Background frequency was determined as the mean of the placebo and month 0 responses plus 3 SD and set at 0.003%. The bars depict the median values and the interquartile ranges.

Fig. 2

Summary of the serum antibody response kinetics. Participants were vaccinated with an unadjuvanted, HPV16 L1 VLP vaccine at months 0, 1, and 6. The HPV16 L1 VLP-specific IgG titers (A) and neutralizing antibody titers (B) were tracked over months 0, 1, 2, 7, and 12. The avidity index (C) was tracked over months 2, 7 and 12. The open circles represent each individual. The bars depict the median values and the interquartile ranges. Statistical values calculated using a Mann-Whitney test between consecutive time points (* p

Fig. 3

Correlation between neutralizing antibody titers and avidity at months 2 (A), 7 (B) and 12 (C). Within each graph the total number of samples used in the analysis is represented by “N”. The Spearman correlation coefficient and p-value are also indicated on each graph.

Fig. 4

Correlation between memory B cell frequencies and measurements of the systemic antibody response in HPV-16 L1 VLP recipients at month 7. Correlations between IgG memory B cell frequencies against HPV16-specific IgG titers (A), neutralizing antibody titers (B) or avidity indices (C). Within each graph the total number of samples used in the analysis is represented by “N”. The Spearman correlation coefficient and p-value are also indicated on each graph.