The production and immunogenicity of human papillomavirus type 58 virus-like particles produced in Saccharomyces cerevisiae

Abstract

Human papillomavirus (HPV) is the cause of most cases of cervical cancer. HPV type 58 (HPV58) is the second most frequent cause of cervical cancer and high-grade squamous intraepithelial lesions (HSIL) in Asia and South / Central America, respectively. However, there is no vaccine against HPV58, although there are commercially available vaccines against HPV16 and 18. In this study, we produced HPV58 L1 protein from Saccharomyces cerevisiae, and investigated its immunogenicity. We first determined the optimum period of culture for obtaining HPV58 L1. We found that a considerable portion of the HPV58 L1 resulting from 48 h culture cannot be recovered by purification, while the HPV58 L1 resulting from 144 h culture is recovered efficiently: the yield of HPV58 L1 finally recovered from 144 h culture was 2.3 times higher than that from 48 h culture, although the production level of L1 protein from 144 h culture was lower than that from 48 h culture. These results indicate that the proportion of functional L1 protein from 144 h-cultured cells is significantly higher than that of 48 h-cultured cells. The HPV58 L1 purified from the 144 h culture was correctly assembled into structures similar to naturally occurring HPV virions. Immunization with the HPV58 L1 efficiently elicited anti-HPV58 neutralizing antibodies and antigen-specific CD4+ and CD8+ T cell proliferations, without the need for adjuvant. Our findings provide a convenient method for obtaining substantial amounts of highly immunogenic HPV58 L1 from S. cerevisiae.

Advances in Designing and Developing Vaccines, Drugs and Therapeutic Approaches to Counter Human Papilloma Virus

“…Moreover, VLPs of HPV-58 with the L1 protein produced in S. cerevisiae elicited antibodies and antigen-specific CD4+ and CD8+ T cell responses without the need for an adjuvant ( 136 ). Also, HPV-16 and -18 L1 protein expressed in E. coli to produce bivalent VLPs has been demonstrated safe and highly immunogenic as a vaccine candidate in preclinical studies ( 137 ).…”

EV71 virus-like particles produced by co-expression of capsid proteins in yeast cells elicit humoral protective response against EV71 lethal challenge

“…In recent years, recombinant virus-like particle (VLP)-based vaccine strategies have been frequently used for novel vaccine design. Vaccines based on viral VLPs have been successfully used in prevention against hepatitis B virus and human papillomavirus [ 21 – 23 ]. VLPs are empty non-infectious viral capsids that structurally mimic the conformation of native virion.…”

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

“…As with Cervarix and Gardasil 4vHPV vaccines, the investigational 3vHPV targets HPV 16 and 18. In addition, like Gardasil9, it is also able to induce significant antibody responses against HPV 58, an HPV strain that is the third most prevalent in East Asia [37] , [38] . Inclusion of HPV 58 in the development of next-generation HPV vaccines, as suggested by Chan [9] , is much desired in East Asia.…”