Case Study: Using cryoEM to characterize 
virus-like particles in GARDASIL®

The challenge

Human papillomavirus (HPV) vaccines based on major capsid protein L1 are licensed in over 100 countries to prevent HPV infections that result in cervical cancer and warts. The yeast-derived recombinant quadrivalent HPV L1 (Types 6, 11, 16, and 18) vaccine GARDASIL has played an important role in reducing cervical cancer since their introduction for human use in 2006.

The L1 proteins expressed in yeast self-assemble into virus-like particles (VLPs) that when properly adjuvanted, elicit protective immune responses by mimicking the authentic epitopes of virions. Routine biochemical techniques can be applied to confirm the primary structure of the proteins in these recombinant vaccines. However, other tools are needed to visualize critical morphological characteristics of these VLP vaccine intermediates.

The solution

Cryo transmission electron microscopy (cryoEM) provides an excellent visualization tool to directly determine morphological characteristics of VLP vaccine intermediates, including shape, particle integrity, and aggregation. It can also be used to observe the VLPs when absorbed onto aluminum adjuvants. 

These data can be combined with the results from orthogonal methods to provide information important for process development, process optimization......

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