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2024-02-29| InterviewsR&D

An Interview with the Inventor of HPV Vaccine, Ian Frazer, Building a Firewall for Public Health

by Oscar Wu
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GeneOnline recently had the privilege of interviewing Professor Ian Frazer, the renowned inventor of the human papillomavirus (HPV) vaccine. During the insightful discussion, Frazer delved into the history and development of the HPV vaccine, a journey that dates back to the early 1980s with the discovery by Harald zur Hausen that HPV genes were present in cervical cancers. This discovery laid the groundwork for further research into the transformation of normal epithelial cells into cancerous cells due to HPV.

The Discovery that Paved the Way

The Human Papillomavirus (HPV) vaccine is a significant medical advancement designed to prevent infections caused by certain types of human papillomavirus. HPV is a common virus that can lead to certain types of cancers later in life, such as cervical cancer, anal cancer, oropharyngeal cancer, and others. The vaccine works by preparing the body’s immune system to recognize and fight the virus if the person is exposed to it.

The Genesis of the HPV Vaccine

Frazer’s interest in the virus was initially piqued by the apparent link between HPV and anal cancer. “I got interested in papillomavirus because I observed that one of the cancers that seemed to be associated with papillomavirus was anal cancer,” he said.

The lack of data on the immunology of the virus was then led him and his colleague Dr. Jian Zhou to engage in genetic engineering, as papillomaviruses proved impossible to cultivate in the lab, “There’s no substrate that you can put 10 viruses in and get more than 10 viruses out”, he said. 

Innovations in Gene Expression

The development of the HPV vaccine marked a significant shift in the approach to gene expression, moving from bacterial expression to the use of the vaccinia vector in eukaryotic cells. 

This pivotal change enabled the successful expression of the virus’s capsid proteins, which led to an unexpected yet crucial discovery: these proteins self-assembled into virus-like particles (VLPs). 

These VLPs are integral to the vaccine’s design, as they mimic the outer shell of the Human Papillomavirus (HPV) but crucially do not contain any viral DNA, eliminating the risk of causing HPV infection or its associated cancers.

The Role of L1 Protein in Vaccine Development

A major component of these VLPs is the L1 protein, the primary capsid protein of HPV. These VLPs, formed by co-expressing HPV16 capsid proteins L1 and L2 in monkey kidney epithelial cells, exhibited a virus-like 3D structure. 

The research utilizing both vaccinia and baculovirus vectors highlighted the importance of the L1 protein in the formation of effective virus-like particles. This breakthrough was a turning point, paving the way for the large-scale production of these particles. Consequently, this led to the licensing and development of the vaccine by pharmaceutical companies Merck and GSK.

Clinical Trials and Vaccine Efficacy Achieving a 99% Efficacy Rate

Contrary to initial beliefs that cervical cancer and HPV infection were relatively rare, the vaccine trials demonstrated a widespread prevalence of HPV. 

The trials showed an impressive 99% efficacy rate in preventing HPV infection and pre-cancerous conditions such as CIN3, underscoring the vaccine’s significant impact on public health.

From Pap Smears to PCR Testing

Frazer also discussed the shift from traditional pap smears to PCR-based automated testing for HPV in countries like Australia, emphasizing the improved accuracy, cost-effectiveness, and adoption of these molecular tests globally. 

The interview further explored the broader impact of the HPV vaccine’s discovery on other vaccines, noting its limited applicability to non-lipid-coated, crystalline viruses.

The Vaccine’s Broader Implications

Moreover, Frazer provided insights into Australia’s biotechnology landscape, highlighting the nation’s proficiency in clinical trials and innovative product development. He emphasized the need for improved scalable manufacturing and government investment in the biotech sector. The discussion also touched on Australia’s potential as a major supplier of GMP-grade materials for Southeast Asia.

In summary, the interview with Professor Ian Frazer offered a comprehensive overview of the journey and implications of the HPV vaccine discovery, including its role in preventing HPV infection and pre-cancerous conditions. It also explores the potential for similar vaccines for other viruses. The widespread use of the HPV vaccine has the potential to greatly reduce the incidence of HPV-related cancers globally. Its adoption and implementation in national immunization programs are vital steps in cancer prevention strategies.

In the end of the interview, GeneOnline and Frazer then focus on the future potential of Australia’s biotechnology industry, highlighting the need for infrastructure, molecular technologies, and government support. They also discuss the challenges faced by Australia in manufacturing and funding for the biotech industry, emphasizing the reliance on government support and the potential for Australia to become a major supplier of GMP raw materials.

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