Release and Stability Testing Programs for a Novel Virus-Like Particle Vaccine

Release testing involves both standard potency assays and unique assays (particle size, NA activity) developed to ensure the physical, chemical, and biological stability of this type of vaccine.
Oct 02, 2010


Virus-like particle (VLP) vaccines are currently used for the prevention of hepatitis B and human papillomavirus infections. Influenza VLPs have been produced using a baculovirus–insect cell production system and shown to be safe and immunogenic in multiple Phase 2 clinical trials. These vaccines present unique challenges in their development in terms of the design of product release assays, product characterization, and stability testing. Methods that have been used to characterize simpler biological drugs (monoclonal antibodies, protein therapeutics) to ensure their potency and consistency have been applied to release and stability testing of VLPs and will be discussed here.

The H1N1 pandemic influenza outbreak has served as a reminder that current approaches to the development and production of vaccines are not sufficient to meet future unexpected needs. There have been three vaccine technologies used for the prevention of human viral disease. Classical live attenuated and inactivated or split vaccines have been used successfully to protect against multiple viruses including smallpox, influenza, measles, mumps, poliovirus, hepatitis A, herpes zoster, and rotavirus. These vaccines have been safe and effective but in some cases their use has been limited, particularly in developing countries, because of cost and requirements for a cold storage chain. Challenges are also seen in the industrialized world, because these types of vaccines require the growth of viral strains which in many cases is carried out in chicken eggs, and the strains do not always grow well in that platform. More recently, recombinant technology has allowed the development of new types of vaccines (subunit proteins, virus-like particles) that do not require the growth of viral agents and are non-infectious.

Virus-Like Particle Vaccines (VLPs)

Live attenuated and inactivated whole virus vaccines are the progenitors of VLPs that are in use today to prevent hepatitis B (Recombivax HB, Engenrix B) and human papillomavirus infections (Gardasil, Cervarix). VLPs contain viral proteins required to generate protective immune responses but are non-infectious and lack the potential to recombine with circulating virus because they lack viral nucleic acid. These vaccines have potential immunologic advantages over split or purified protein vaccines because: 1) VLPs contain multiple copies of antigens presented in an organized array, thus allowing activation of the innate immune system and 2) the size of VLPs allows efficient uptake and processing by dendritic cells, which are the antigen presenting cells of the immune system and stimulate lymphocytes in lymph nodes.