Substantial progress has been made towards the eradication of polio through the use of two different vaccines: the inactivated poliovirus vaccine (IPV) and the attenuated oral poliovirus vaccine (OPV). OPV has been useful in eradicating polio from most of the world, due to its simplicity of administration, development of herd immunity resulting from excretion, ease of production, and low cost. Unfortunately, use of OPV in developing countries often requires up to 10 immunizations to achieve equivalent protective levels of immunity compared to children in developed countries. A number of groups have proposed replacing OPV with IPV as part of the final polio eradication campaign. Unfortunately, IPV is more expensive than OPV and does not induce heard immunity or mucosal protection. There are number of potential approaches for improving the immunogenicity and efficacy of IPV and other vaccines, including alternate delivery routes (e.g., intradermal or sublingual) and the use of nano-scale delivery systems. A number of micro- and nano-carriers have been developed that may be appropriate for vaccine delivery, including liposomes, micro-, nano-, and multiple-emulsions, polymeric nano- particles, dendrimers, and immunostimulatory complexes (ISCOMS). Our own nano- and micro-scale technology vaccine delivery research over the last five years has led us to appreciate the potential of nano- carriers to enhance the immunogenicity and efficacy of multiple vaccines by different routes of immunization. For this project, our primary focus will be on the use of nano-scale carriers to facilitate intradermal and sublingual delivery of IPV, building upon our earlier findings. The proposed studies will address important questions in vaccine delivery by application of nano-technology through the exploitation of the novel properties of nano-carriers. The findings of these studies will be broadl applicable to a variety of vaccines and will further highlight the important role of nano-technology in science and medicine.
The specific aims are 1) Optimize the incorporation and stability of IPV within specialized nano-carriers;2) Evaluate the ability of the nano-carrier formulations to enhance production of serum and mucosal antibodies and neutralizing antibodies against all three serotypes of poliovirus following intradermal or sublingual immunization in a murine model;3) Evaluate the ability of the nano-carrier formulations to enhance the immunologic responses to fractional doses of IPV following intradermal or sublingual immunization in a murine model;4) Evaluate the effect of pre-existing antibodies against IPV on the immune responses to IPV formulated in the different nano-carriers following intradermal or sublingual immunization in a murine model, and 5) Evaluate serum and mucosal, humoral and cellular responses following intradermal or sublingual immunization with IPV formulated in the optimum nano-carrier for each route in non-human primates.
In this project, we will test the hypothesis that appropriately formulated nano-carriers can enhance the immune response to inactivated poliovirus vaccine (IPV) when delivered just under the skin (intradermally) or placed beneath the tongue (sublingually). This strategy is designed to improve the immunogenicity and effectiveness of IPV and facilitate the use of IPV as part of the final polio eradication campaign. The findings of thes studies will be broadly applicable to a variety of vaccines and will further highlight the importan role of nano- technology in science and medicine.
|Norton, Elizabeth B; Branco, Luis M; Clements, John D (2015) Evaluating the A-Subunit of the Heat-Labile Toxin (LT) As an Immunogen and a Protective Antigen Against Enterotoxigenic Escherichia coli (ETEC). PLoS One 10:e0136302|