Designing Recombinant Vaccines with Viral Properties: A Rational Approach to More Effective Vaccines

Abstract

One of the great demands and challenges for vaccination is to successfully target the pathogens responsible for much of mankind's chronic disease burden including: AIDS, infectious hepatitis, tuberculosis and malaria. Another is realizing the potential of therapeutic immunization to cure diseases such as cancer, allergy and inflammatory autoimmunity. To achieve these objectives, the fundamental insights gained from immunology, genomics, molecular-cellular biology and vaccinology must be implemented in order to develop more effective, better defined and safer vaccines. As an illustrative example of this we examine the key features of viruses that are known to be responsible for eliciting superb host immune responses. These insights have formed a basis for understanding the effectiveness of existing vaccines and provide a framework for designing and developing new vaccines better able to meet pressing unmet medical needs. The key immunogenic properties of viruses that are understood to date and are currently being applied include: their particulate nature, their highly repetitive and ordered structures, their ability to induce innate immunity with consequent conditioning of adaptive responses and the kinetics and distribution of viral antigens during infection. Vaccines and vaccine-formulations recently registered for use in humans already incorporate some of these elements. Of great anticipation is the progress of the next-generation vaccines now advancing through the various stages of research and development. Vaccines which, by way of rational design, incorporate viral properties to induce tailored responses and thus have the potential to provide safer and more effective prophylaxis and therapies.

Virus-Like Display of a Neo-Self Antigen Reverses B Cell Anergy in a B Cell Receptor Transgenic Mouse Model

“…Presentation of a self-Ag at high density on either platform makes self-Ags as antigenic as a foreign Ag presented in the same context (11)(12)(13). These data have raised the possibility that VLP-based vaccines may be effective at inducing Ab responses that could modulate self-Ags involved in chronic diseases, and currently VLP-based vaccines that target angiotensin II (for hypertension), amyloid-␤ (Alzheimer's disease), ghrelin (obesity), and TNF-␣ (psoriasis), among others, are in clinical trials (10,14).…”

Engineering of virus-like particles for alternative vaccine candidate targeting a hypervariable peptide antigen element

“…One emerging technology that has a potential as the nextgeneration of influenza vaccines is the virus-like particle (VLP). VLP represents an advanced vaccine technology platform, which is able to combine most of the key features of viruses (1) highly repetitiveness, (2) particulate nature, and (3) effective induction of innate immune response leading to strong T-cell responses (Jennings and Bachmann 2007).…”

“…Studies in modular VLPs presume that it is nearly impossible for a peptide antigen element to assume its conformational integrity when it is presented on a modular VLP (Jennings and Bachmann 2007, Tissot et al 2010. Until now, presentation of a peptide antigen element on a modular VLP and the impact of display strategy for presentation of the antigen element on the quality of the resulting antibodies are not fully understood.…”

“…Thus, in order to obtain antibodies that cross-react with the native antigen protein, the epitope peptides need to maintain conformational integrity (Purcell et al 2007, Purcell et al 2003). The quality of antibodies has been shown to resemble the protection efficacy of the antibodies (Alvarez et al 2010 A higher antibody quality indicates a higher potential of protection efficacy, thus a high quality of antibodies is desirable.Studies in modular VLPs presume that it is nearly impossible for a peptide antigen element to assume its conformational integrity when it is presented on a modular VLP (Jennings and Bachmann 2007, Tissot et al 2010. Until now, presentation of a peptide antigen element on a modular VLP and the impact of display strategy for presentation of the antigen element on the quality of the resulting antibodies are not fully understood.…”

What rough beast? Synthetic biology, uncertainty, and the future of biosecurity

“…Design of vaccines to combat such agents requires engineering features that enable the vaccine to generate a more potent immune response. 72 SB techniques provide an ideal toolbox to accomplish this goal. Engineered adjuvants -that is, chemicals added to a vaccine to magnify the immune response it provokes -might also be generated more effectively using SB techniques.…”