Differential Antibody Response against Conformational and Linear Epitopes of the L1 Proteins from Human Papillomavirus Types 16/18 Is Observed in Vaccinated Women or with Uterine Cervical Lesions.

Lourdes Gutierrez-Xicotencatl,Minerva Maldonado-Gama,Adolfo Pedroza-Saavedra,Azucena Salazar-Piña,Aurelio Cruz-Valdez,Fernando Esquivel-Guadarrama,Lilia Chihu-Amparan,Aislinn Citlali Perez-Morales,Angelica Nallelhy Rodriguez-Ocampo

doi:10.3390/vaccines9050442

Lourdes Gutierrez-Xicotencatl, Minerva Maldonado-Gama + Show 7 more

Open Access

https://doi.org/10.3390/vaccines9050442

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Abstract

Antibodies against the Human Papillomavirus (HPV) L1 protein are associated with past infections and related to the evolution of the disease, whereas antibodies against L1 Virus-Like Particles (VLPs) are used to follow the neutralizing antibody response in vaccinated women. In this study, serum antibodies against conformational (VLPs) and linear epitopes of HPV16/18 L1 protein were assessed to distinguish HPV-vaccinated women from those naturally infected or those with uterine cervical lesions. The VLPs-16/18 were generated in baculovirus, and L1 proteins were obtained from denatured VLPs. Serum antibodies against VLPs and L1 proteins were evaluated by ELISA. The ELISA-VLPs and ELISA-L1 16/18 assays were validated with a vaccinated women group by ROC analysis and the regression analysis to distinguish the different populations of female patients. The anti-VLPs-16/18 and anti-L1-16/18 antibodies effectively detect vaccinated women (AUC = 1.0/0.79, and 0.94/0.84, respectively). The regression analysis showed that anti-VLPs-16/18 and anti-L1-16/18 antibodies were associated with the vaccinated group (OR = 2.11 × 108/16.50 and 536.0/49.2, respectively). However, only the anti-L1-16 antibodies were associated with the high-grade lesions and cervical cancer (CIN3/CC) group (OR = 12.18). In conclusion, our results suggest that anti-VLPs-16/18 antibodies are effective and type-specific to detect HPV-vaccinated women, but anti-L1-16 antibodies better differentiate the CIN3/CC group. However, a larger population study is needed to validate these results.

Highlights

Cervical cancer (CC) is the fourth-most common cancer worldwide [1]
To distinguish Human Papillomavirus (HPV)-vaccinated women from naturally infected ones or from those that had developed uterine cervical lesions or CC, we evaluated the presence of HPV16 and HPV18 anti-Virus-Like Particles (VLPs) and anti-L1 antibodies in the serum of these women
The analysis showed that anti-VLPs-16/18 antibodies were highly associated with the HPV-vaccinated women (OR = 2.11 × 108 and 16.50, respectively) (p ≤ 0.001) and, to a lesser extent, with the CIN3/CC group (OR = 2.29, for antiVLPs-16), albeit without statistical significance (Table 2)

Summary

Introduction

In developing countries like Mexico, CC occupies the third place, and it represents an important public health problem. In 2018, about 569,800 women were diagnosed with CC around the world, and 84% of them corresponded to underdeveloped countries [1]. Human Papillomavirus (HPV) is the etiological agent of CC, and high-risk HPV types 16 and 18 are the most frequently present in this pathology worthwhile and, in Mexico [2,3]. The L1 protein is able to self-assemble in different cellular systems in vitro to produce highly immunogenic VirusLike Particles (VLPs), which are used in HPV vaccines [4,5], as they generate a protective humoral immune response [6,7]

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