A novel trivalent HPV 16/18/58 vaccine with anti-HPV 16 and 18 neutralizing antibody responses comparable to those induced by the Gardasil quadrivalent vaccine in rhesus macaque model

Abstract

Persistent infection with human papillomavirus (HPV) is a key factor in the development of precancerous lesions and invasive cervical cancer. Prophylactic vaccines to immunize against HPV are an effective approach to reducing HPV related disease burden. In this study, we investigated the immunogenicity and dosage effect of a trivalent HPV 16/18/58 vaccine (3vHPV) produced in Escherichia coli (E.coli), with Gardasil quadrivalent vaccine (4vHPV, Merck & Co.) as a positive control. Sera collected from rhesus macaques vaccinated with three dosage formulations of 3vHPV (termed low-, mid-, and high-dosage formulations, respectively), and the 4vHPV vaccine were analyzed by both Pseudovirus-Based Neutralization Assay (PBNA) and Enzyme-Linked Immunosorbent Assay (ELISA). Strong immune responses against HPV 16/18/58 were successfully elicited, and dosage-dependence was observed, with likely occurrence of immune interference between different L1-VLP antigens. HPV 16/18 specific neutralizing antibody (nAb) and total immunoglobulin G (IgG) antibody responses in rhesus macaques receiving 3vHPV at the three dosages tested were generally non-inferior to those observed in rhesus macaques receiving 4vHPV throughout the study period. Particularly, HPV 18 nAb titers induced by the mid-dosage formulation that contained the same amounts of HPV 16/18 L1-VLPs as Gardasil 4vHPV were between 7.3 to 12.7-fold higher compared to the positive control arm from weeks 24–64. The durability of antibody responses specific to HPV 16/18 elicited by 3vHPV vaccines was also shown to be non-inferior to that associated with Gardasil 4vHPV.

Cross-neutralizing antibody titres against non-vaccine types induced by a recombinant trivalent HPV vaccine (16/18/58) in rhesus macaques

“…Gardasil was chosen as the positive control, which contained the same amounts of HPV16/18 L1-VLPs as middle dose KLWS 3v vaccine but less adjuvant (225 μg of aluminum hydroxyphosphate sulfate per dose). They were intramuscular injection to groups of female rhesus macaques (n = 5) aged 3–5 in a 0, 4 and 24 week [ 43 ].…”

Principais fatores de risco associados ao desenvolvimento do câncer de colo do útero, com ênfase para o Papilomavírus humano (HPV): um estudo de revisão

“…Diante do exposto, pode-se observar uma grande variabilidade de fatores interligados a etiologia do CCU, podendo ser citados: As infecções pelo vírus Herpes simples tipo II, (Santos et al, 2010), o uso de corticoides (Casarin & Piccoli, 2011), multiplicidade em parceiros (Costa et al, 2011), tabagismo (Dos Anjos et al, 2013), a baixa ingestão de vitaminas (Leite et al, 2014), baixa condição socioeconômica (De Souza & Costa, 2015), Uso de anticoncepcionais (Almeida & Assis, 2017), infecção pelo HPV (Yin F et al, 2017), práticas homossexuais e bissexuais (Crispim et al, 2018), início precoce da atividade sexual (Zandonade et al, 2018) Martínez et al, (2015) descrevem três tipos de biopsia: biópsia colposcópica, curetagem endocervical e biópsia de cone (procedimento eletro cirúrgico de alça e biópsia de cone de faca fria). A biópsia colposcópica realiza uma seção na superfície da região anômala para verificar a histologia do tecido.…”

Ongoing challenges and future directions of human papillomavirus vaccination

“…В настоящее время разрабатываются новые профилактические вакцины, например трехвалентная вакцина против ВПЧ 16, 18 и 58 типов, предназначенная для Азиатско-Тихоокеанского региона. Несмотря на то что ВПЧ 58 типа редко встречается в большинстве стран мира, в Южной Корее, Японии и Китае он занимает третье место среди типов ВПЧ, ассоциированных с раком шейки матки [50].…”