SBIR Phase I: Development of Bacteriophage Qbeta and Mutants as Carriers for Next Generation Vaccines

This SBIR Phase I project aims to develop an anti-cancer vaccine. A successful vaccine against cancer can potentially revolutionize cancer treatment and prevention by providing durable protection to patients and preventing relapse, without the harmful side effects commonly associated with chemo- and radiation- therapies. One of the major challenges in anti-cancer vaccine development is the low immunogenicity of cancer antigens, in particular tumor associated carbohydrate antigens. In order to overcome this, in this project, a new carrier system based on bacteriophage Qbeta will be developed. A representative carbohydrate antigen GD2 will be linked with bacteriophage Qbeta, which can elicit superior titers of antibodies that can kill cancer cells. Successful commercial development of such vaccines will greatly benefit cancer patients not only in the US, but also throughout the world. In addition to cancer vaccines, the bacteriophage Qbeta based carrier is a new platform technology to elicit powerful antibody responses. Biotechnological companies interested in vaccine development can adapt Qbeta as the carrier to target infectious diseases and chronic diseases. Furthermore, the Qbeta platform can provide an excellent starting point for the generation of monoclonal antibodies, which are among the top agents developed for therapeutics and diagnostics. Thus, the availability of a superior carrier can potentially address a wide range of biomedical needs. This SBIR Phase I project proposes to design new bacteriophage Qbeta based carriers for next generation vaccines. Vaccines have had tremendous impacts on public health. Traditional vaccines commonly incorporate attenuated or killed bacteria or viruses as immunogens. With the enhanced requirements on safety, the field is focusing more on well-defined subunits as epitopes for vaccine design. As subunits tend to have lower immunogenicity, immunogenic carriers are critical to deliver the desired antigen to the immune system and to enhance the immune responses. However, there are only a few carriers available that have been validated in clinical studies. The limited choices of carriers can significantly reduce vaccine efficacy due to interferences from anti- carrier antibodies. This project develops a new class of immunogenic carrier based on bacteriophage Qbeta capable of eliciting superior levels of IgG antibodies to the target antigen compared to gold standard carrier proteins. Novel mutants of Qbeta will become available to elicit high levels of IgG antibodies against the target antigen. The utility of the new Qbeta carrier will be demonstrated in delivering a tumor associated carbohydrate antigen, i.e., ganglioside GD2 derivative, to induce potent anti-cancer IgG antibodies. When successful, the GD2 based vaccine will be a quantum leap for the field as it will be the first ever carbohydrate based anticancer vaccine. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.