ABSTRACT
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)
(VETTER PHARMA INTERNATIONAL GMBH)
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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.
