Human Papillomavirus 16 (HPV 16) and HPV 18 Antibody Responses Measured by Pseudovirus Neutralization and Competitive Luminex Assays in a Two- versus Three-Dose HPV Vaccine Trial

Krajden, Mel; Cook, Darrel; Yu, Amanda; Chow, Ron; Mei, Wendy; McNeil, Shelly; Money, Deborah; Dionne, Marc; Karunakaran, K. P.; Palefsky, Joel M.; Dobson, Simon; Ogilvie, Gina; Petric, Martin

doi:10.1128/cvi.00489-10

Cited by 49 publications

(38 citation statements)

References 13 publications

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“…3 Such potent and consistently high immune response in younger girls lead to the hypothesis that less than 3 doses of the vaccine might offer enough protection in girls aged below 15 y A number of randomized and non-randomized studies demonstrated that the antibody response elicited by 2 doses administered at least 6 months apart in adolescent girls was non-inferior to that elicited by 3 doses of the HPV vaccine. [4][5][6][7] The earliest evidence on the protective effect against infection of less than 3 doses of the vaccine was put forward by the posthoc analysis of the results of some of the phase III efficacy trials of the bivalent vaccine (2vHPV) in which some of the girls/ women received single or 2 doses by default. 8 The results also provided the early but exciting indication that even single dose of the vaccine might be effective.…”

Section: Introductionmentioning

confidence: 99%

Less than 3 doses of the HPV vaccine – Review of efficacy against virological and disease end points

Basu

Bhatla

Ngoma

et al. 2016

Human Vaccines & Immunotherapeutics

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World Health Organization (WHO) recommended 2 doses of the Human Papillomavirus (HPV) vaccine for girls below 15 y on the basis of the immune-bridging studies demonstrating non-inferior immune response of 2 doses in the adolescent girls compared to 3 doses in the young adult women in whom the efficacy against disease is established. The biological nature of the antigens (virus-like particles) constituting the HPV vaccine is responsible for the vigorous antibody response that may make the third dose redundant. The protection offered by 2 doses has been demonstrated in non-randomized clinical trials to be comparable to that offered by 3 doses against incident and persistent infections of vaccine targeted HPV types. However, results emerging from the ecological and nested case-control studies embedded in the population based screening programs of different countries indicate reduced efficacy of 2 doses against virological and disease end points. Some recent studies observed the protective effect of single dose of the vaccine against incident and persistent infections of the vaccine targeted HPV types to be similar to 3 doses in spite of immunological inferiority. The sample size, duration of follow-ups and number of events were limited in these studies. Longer follow ups of the less than 3 doses cohorts in the ongoing studies as well as appropriately designed and ethically justifiable randomized studies are needed to establish the protection offered by the alternative schedules at least beyond 10 y of vaccination.

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Section: Introductionmentioning

confidence: 99%

Less than 3 doses of the HPV vaccine – Review of efficacy against virological and disease end points

Basu

Bhatla

Ngoma

et al. 2016

Human Vaccines & Immunotherapeutics

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“…In addition to platform and format differences, these assays use different reference standards that report in different units and use serostatus cutoffs that were developed using different methods. Thus far direct comparisons between these assays have been sparse (9)(10)(11). The limited understanding of how these assays relate to each other in the context of unvaccinated populations/natural infection makes comparison across studies complex.…”

Section: Introductionmentioning

confidence: 99%

Direct Comparison of HPV16 Serological Assays Used to Define HPV-Naïve Women in HPV Vaccine Trials

Safaeian

Ghosh

Porras

et al. 2012

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Two HPV serological assays, the competitive Luminex immunoassay (cLIA), and an enzymelinked immunoassay (ELISA) against HPV16 have been used to define HPV-na€ ve subcohorts within large HPV vaccination trials. Some of the variation in estimated vaccine efficacies may be due to the differences in these assays used to define the HPV-na€ ve subgroups. To guide the interpretation of published results, we compared these assays.Methods: Replicate enrollment sera from a stratified sample of 388 unvaccinated women from the control arm of the Costa Rica HPV 16/18 Vaccine Trial were measured for antibodies against HPV16 using cLIA and ELISA. Agreement between the assays was estimated using standard and alternative assay cutoffs.Results: Using laboratory-determined seropositivity cutoffs, sampling-adjusted HPV16 seropositivity was 24.8% by ELISA and 7.2% by cLIA. Comparing cLIA and ELISA antibody levels based on the standard cutoffs, overall agreement was 53% (positive-agreement ¼ 49%). The poor agreement was mainly driven by the higher sensitivity of the ELISA than cLIA, resulting in 30% of the ELISA-positive sample that were cLIA-negative (none of the ELISA-negatives were cLIA-positive). Increasing ELISA cutoff to 54 ELISA units (EU)/mL (the level which maximized agreement with cLIA; ELISA standard cutoff is 8 EU/mL) resulted in higher agreement (overall agreement ¼ 91%; positive agreement ¼ 78%).Conclusions: ELISA and cLIA are different from each other based on the laboratory-determined cutoff. Increasing ELISA cutoff increased agreement with cLIA, which could facilitate comparisons among studies that use different assays.Impact: Keeping cLIA at the laboratory-determined cutoff but altering ELISA cutoff for seropositivity might facilitate vaccine efficacy comparisons in the na€ ve cohorts defined by cLIA. Cancer Epidemiol Biomarkers Prev; 21(9); 1547-54. Ó2012 AACR.

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“…L1 VLP immunizations were carried out using a relatively small number of animals, and while all three constructs induced neutralizing antibodies against all three variant PsVs, the variability inherent in using small groups of animals may have concealed subtle differences in immunogenicity. Although HPV L1L2 PsVs have been used widely to monitor antibody responses to vaccines and natural infection (22,47,48,60), as well as elucidate steps in the entry process (61)(62)(63)(64), there are likely to be some differences between how these behave in vitro and how authentic HPV31 lineage variants behave in vivo, although this is a limitation of most PsV-based systems.…”

Section: Discussionmentioning

confidence: 99%

“…A degree of vaccine-induced cross-protection against closely related genotypes, particular HPV31, HPV33, and HPV45, has also been demonstrated (16)(17)(18). HPV vaccine type-specific protection is assumed to be mediated by L1-neutralizing antibodies, which can be detected in the serum and cervicovaginal secretions of vaccinees (16,(19)(20)(21)(22). The role of L1-neutralizing antibodies in mediating cross-protection is less clear, although a recent study reported an association between the presence of HPV31 cross-neutralizing antibodies and a reduced risk of HPV31 infection (23).…”

mentioning

confidence: 99%

Naturally Occurring Capsid Protein Variants of Human Papillomavirus Genotype 31 Represent a Single L1 Serotype

Bissett

Godi

Fleury

et al. 2015

J Virol

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We investigated naturally occurring variation within the major (L1) and minor (L2) capsid proteins of oncogenic human papillomavirus (HPV) genotype 31 (HPV31) to determine the impact on capsid antigenicity. L1L2 pseudoviruses (PsVs) representing the three HPV31 variant lineages, variant lineages A, B, and C, exhibited comparable particle-to-infectivity ratios and morphologies. Lineage-specific L1L2 PsVs demonstrated subtle differences in susceptibility to neutralization by antibodies elicited following vaccination or preclinical L1 virus-like particle (VLP) immunization or by monoclonal antibodies; however, these differences were generally of a low magnitude. These data indicate that the diagnostic lineage-specific single nucleotide polymorphisms within the HPV31 capsid genes have a limited effect on L1 antibody-mediated neutralization and that the three HPV31 variant lineages belong to a single L1 serotype. These data contribute to our understanding of HPV L1 variant antigenicity. IMPORTANCEThe virus coat (capsid) of the human papillomavirus contains major (L1) and minor (L2) capsid proteins. These proteins facilitate host cell attachment and viral infectivity and are the targets for antibodies which interfere with these events. In this study, we investigated the impact of naturally occurring variation within these proteins upon susceptibility to viral neutralization by antibodies induced by L1 VLP immunization. We demonstrate that HPV31 L1 and L2 variants exhibit similar susceptibility to antibody-mediated neutralization and that for the purposes of L1 VLP-based vaccines, these variant lineages represent a single serotype. Human papillomaviruses (HPVs) have a double-stranded DNA genome of approximately 8 kb which is replicated via host cell polymerases with an error rate of ca. 2 ϫ 10 Ϫ8 base substitutions per site per year (1), substantially lower than that found in the majority of single-stranded RNA viruses (ca. 1 ϫ 10 Ϫ3 base substitutions per site per year) (2). Despite the low evolutionary rate of the HPV genome, variants have arisen over time, leading to the generation of distinct intragenotype lineages classified by a sequence difference of 1 to 10% across the whole genome (3). The single nucleotide polymorphisms (SNPs) that allow segregation of these variants into distinct lineages can be found in each gene/ region, with the highest number accumulating in the noncoding regions (NCR1, NCR2, and URR) and the lowest number accumulating in structural (L1 and L2) genes (4).The HPV structural genes encode the major (L1) and minor (L2) proteins that form the nonenveloped icosahedral viral capsid, which comprises 72 pentameric L1 capsomers, and each capsomer has an upper estimate of one L2 protein (5). The L1 protein mediates attachment to host cells (6), while the L2 protein is essential for subsequent viral infectivity (7).The humoral immune response following natural HPV infection predominately targets conformational epitopes on the surface-exposed loop regions of the L1 protein (8, 9). Seroconvers...

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Human Papillomavirus 16 (HPV 16) and HPV 18 Antibody Responses Measured by Pseudovirus Neutralization and Competitive Luminex Assays in a Two- versus Three-Dose HPV Vaccine Trial

Cited by 49 publications

References 13 publications

Less than 3 doses of the HPV vaccine – Review of efficacy against virological and disease end points

Less than 3 doses of the HPV vaccine – Review of efficacy against virological and disease end points

Direct Comparison of HPV16 Serological Assays Used to Define HPV-Naïve Women in HPV Vaccine Trials

Naturally Occurring Capsid Protein Variants of Human Papillomavirus Genotype 31 Represent a Single L1 Serotype

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