Virus-Like Particle Vaccines: A Nanotechnology Approach to Design Particulate Vaccines for Influenza and Human Papillomavirus
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AuthorBraz Gomes, Kimberly
MetadataShow full item record
TitleVirus-Like Particle Vaccines: A Nanotechnology Approach to Design Particulate Vaccines for Influenza and Human Papillomavirus
AbstractCurrent licensed vaccines against Influenza and the human papillomavirus (HPV) suffer from several limitations. In the case of influenza, the virus has a high rate of mutation and thus inactivated virus vaccines are modified each year in a process that requires 6-8 months. The vaccines are also administered using needle that reduces patient compliance due to pain associated with injections. Most vaccines have cold-chain requirements, which creates a major barrier for transport and storage. In an attempt to overcome these limitations, we investigated a) an alternate route of administration, b) a recombinant conserved antigenic protein from the influenza virus and c) a spray-drying method for producing a micro particulate dry powder influenza vaccine. Our first study conducted in rats used a hollow microneedle injector to deliver a spray-dried inactivated virus vaccine painlessly through the skin. We found an increase in both humoral (elevated IgG) and cellular immunity (Th2 response) in transdermally vaccinated rats that was equal to that of rat’s vaccinated using conventional intramuscular injection. Taking into account the results of this study, our second aim evaluated an alternative recombinant antigen, the matrix-2 protein virus-like particle (M2e VLP), a highly conserved peptide found in the influenza virus. The M2e VLP with immunopotentiating compounds (Alhydrogel® and MPL-A® respectively) showed high expression of important cellular proteins involved in the interaction between DCs and T cells, eventually leading to robust immune responses. The confirmation of antigen presentation (MHC I/MHC II, B7-1 – CD28, CD40 – CD154, LFA-1 – ICAM-1) and IL-12 release indicated that the M2e VLP was highly immunogenic that led us to our final aim, which was to evaluate if the M2e VLP vaccine was protective against a variant strain of influenza [A/Phillipines/2/82 (H3N2)]. With the addition of adjuvants, mice vaccinated with the M2e VLP + MPL-A® and Alhydrogel® showed significantly lower levels of virus load in the lung, suggesting that the vaccine was highly effective and protective. The results from our influenza studies show that the M2e VLP, when spray-dried and delivered through the skin is a great candidate for a potential universal vaccine against influenza. In the case of HPV vaccines, it shares some of the same limitations as influenza, which include need for cold-chain storage, and administration using injections. One of the major limitations of HPV vaccines is cost, which makes it unaffordable for use in developing countries, which have the highest rate of cervical cancer. Our goal was to use the spray drying method to develop a stable, effective and inexpensive vaccine against HPV. Current HPV vaccines utilize VLPs against subtypes of the L1 major capsid protein in the virus. We employed the use of the HPV 16 L1 VLP and encapsulated it into a polymer matrix, yielding microparticles in a dry powdered form. The vaccine was found to be highly immunogenic, seen by the presence of IgG antibodies over a 40 week period, indicating long-term immunity. The spray-drying method for vaccine production yields a dry powder of the vaccine that makes it easy for transportation and packing, eliminating the need for cold-chain storage. Current vaccines are administered as liquid dosage forms which require cold-chain to maintain stability during storage. This makes transport and packaging a significant challenge that often leads to substantial vaccine loss. To reduce the use of painful injections for vaccine administration, the skin is an excellent route that uses the dermal immune system to stimulate robust immune responses. The use of microneedles offers an alternative method for self-administration of vaccines onto the skin, which is particularly significant for vaccination programs in developing countries. These important considerations led us to successfully develop, a) a potential subunit universal vaccine against influenza and b) a highly stable, inexpensive and effective vaccine against HPV.