Chapter 7. Virus-like Particle-based Vaccines: GARDASIL®

Papillomaviruses are widely distributed in Nature among mammals where infection of humans, cattle, dogs, rabbits, monkeys, and other species is typically asymptomatic, but may cause small benign tumors known as papillomas or warts, or even carry a risk of becoming cancerous. The viral particles for more than 100 papillomavirus types are about 55–60 nm in diameter and are composed mostly of the type-specific major capsid protein (L1). Prophylactic human papillomavirus (HPV) vaccines are based on the use of the L1 protein expressed in heterologous expression systems to create self-assembled non-infectious virus-like particles (VLPs) that display immunodominant type-specific neutralizing epitopes. To date, three HPV vaccines have been developed and approved: GARDASIL®, a quadrivalent vaccine, and GARDASIL® 9, a nonavalent vaccine, both made by Merck & Co., Inc., Kenilworth, NJ, USA (MSD), and Cervarix™, a bivalent vaccine made by GlaxoSmithKline. This chapter focuses on the key stages of development of the processes used to support the clinical program and subsequent commercial manufacture of GARDASIL®. Cross-functional collaboration between product development teams was critical for the establishment of a commercially sustainable platform manufacturing process.