1. 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
- Author
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Wang Yajun, Liu Yongjiang, Yefeng Qiu, Zhang Haijiang, Dunquan Jiang, Mei Yan, Wang Yan, Chen Jianping, Yin Fei, and Na Chen
- Subjects
0301 basic medicine ,3vHPV, trivalent HPV 16/18/58 vaccine ,Human papillomavirus ,HPV, human papillomavirus ,Ig, Immunoglobulin ,Trivalent ,Article ,Neutralization ,lcsh:Infectious and parasitic diseases ,DMEM, Dulbecco's Modified Eagle's Medium ,03 medical and health sciences ,nAb, neutralizing antibody ,0302 clinical medicine ,Immune system ,Antigen ,AH, Aluminum Hydroxide ,Virology ,HCP, Host cell protein ,Medicine ,lcsh:RC109-216 ,HPV 16/18/58 ,030212 general & internal medicine ,PBNA, Pseudovirus-Based Neutralization Assay ,Neutralizing antibody ,ELISA, Enzyme-Linked Immunosorbent Assay ,4vHPV, Gardasil quadrivalent vaccine ,GFP, green fluorescent protein ,biology ,business.industry ,Gardasil ,Immunogenicity ,virus diseases ,biology.organism_classification ,PBS, Phosphate-buffered saline ,Titer ,Rhesus macaque ,030104 developmental biology ,Infectious Diseases ,Immunology ,biology.protein ,business ,GMTs ,GMT, Geometric Mean Titer ,medicine.drug - 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 24â64. 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. Keywords: Human papillomavirus, HPV 16/18/58, GMTs, Trivalent, Immunogenicity
- Published
- 2017