Production of chimeric HPV-HIV vaccine in yeast

2017 edition

Yoshiki Eto

Introduction

Human papillomavirus (HPV) and human immunodeficiency virus (HIV) are both sexually transmitted pathogens that cause serious global health problems in both developed and developing countries. For instance, HPV is the main cause of cervical cancer and HIV infection leads to acquired immunodeficiency syndrome (AIDS) over time. In developing nations, cervical cancer is often the most common cause of cancer-related death among women and a leading cause of death overall. Over 95% of HIV infections are happening in underdeveloped nations, and two-thirds of them are in sub-Saharan Africa where more than 28 million people are living with HIV.

Currently, three HPV vaccines are licensed and all of them are based on virus-like particles (VLPs), which resemble viruses but are not infectious because they do not contain any viral genetic material. Therefore, they would be much safer than conventional vaccines such as live attenuated and inactivated ones, which could return to be virulent by mutation or insufficient inactivation. However, these three are still prohibitively expensive for most of the women in developing nations, and the cervical cancer caused by HPV is a lasting menace in those areas.

Nowadays, we can control HIV infection much better than before thanks to HIV drugs, but the cost of daily medications for HIV infection is not affordable to everybody. Furthermore, while HIV vaccine has been investigated for over 30 years, we still do not have any vaccine against HIV.

Thus, safe, effective and affordable vaccines against HPV and HIV are immediately needed. In addition, preventing the mucosal entry of the virus is crucial to prevent HPV and HIV infection. In my thesis project, I am developing a chimerical VLP-based HPV-HIV vaccine by using yeast.

Yeast expression system was chosen because it has great potential to produce recombinant proteins, which could be vaccine candidates. It has already been used to produce licensed vaccines and it can grow rapidly in simple and inexpensive media while expressing high level of proteins.

Hypothesis

Both HPV and HIV are sexually transmitted infections and one of the main access routes of these viruses is the mucosal genital tract. Therefore, the development of a bivalent vaccine which would protect against HPV and HIV infections is a logical effort in the fight against these two major global pathogens. Moreover, through yeast expression system, it could lower the cost of vaccines so that even the people in developing countries can afford them.