In 2008, based on a recommendation by the 9/11 Commission, a bipartisan Commission on the Prevention of Weapons of Mass Destruction Proliferation and Terrorism was created to: (1) assess the nation’s current activities and capabilities to prevent WMD proliferation and terrorism; and (2) provide concrete recommendations for addressing these threats in the future. Bob Graham (D-FL) and Jim Talent (R-MO) chaired the commission, which released their report, World at Risk, 2008. In this report, the Commission predicted that a terrorist event involving a biologic weapon would take place before 2013. The commission urged the nation to develop tools to counter that threat.

Two years later, Graham and Talent submitted a report card assessing the U.S. Government’s progress in protecting the United States from WMD. Pointing to very real delays and problems encountered during the national response to the H1N1 influenza pandemic, which highlighted very important weaknesses in the national preparedness system, Graham and Talent gave U.S. bio-defense preparedness an F.

According to the authors, detection and diagnosis capabilities are the first links in the biodefense preparedness chain, followed by: providing actionable information to federal, state, and local leaders and the general public; having adequate supplies of appropriate medical counter-measures; quickly distributing those countermeasures; access to treatment facilities; protecting the well through vaccines and prophylactic medications; and in certain cases, environmental cleanup. According to the WMD report card, “the United States is seriously lacking in each of these vital capabilities”.

The Proposed Solution

What could be done about the situation immediately? Prioritize and accelerate the development of safer, more effective vaccines. How could that be done? EpiVax has developed and validated a method for vaccine development called “genome-derived epitope-driven vaccines” that is fast, efficient, cheap, and safe. In the cancer vaccine field, a similar approach for vaccine design is well accepted and number of epitope-driven cancer vaccines have successfully passed preclinical tests and are either currently in Phase I/II clinical trials or trials are soon to be initiated.  The genome-derived, epitope-driven vaccine (GD-EDV) approach to developing vaccines for bioterror pathogens is well developed, has achieved proof of principle, is being used (under discretionary funding) at the Department of Defense in the laboratories of DoD vaccine development experts.

GD-ED Vaccines

As outlined by EpiVax, the critical components of a vaccine is summarized as follows:

Immunogen + Adjuvant + Delivery vehicle = Vaccine.

Adjuvants and delivery vehicles abound, but the discovery and production of effective immunogens, the substance responsible for stimulating an immune response, have proven difficult to accelerate and methods for producing antigens (including egg-based culture for influenza) are -antiquated and laborious. A better method of making “faster vaccines” is to design immunogens directly from the pathogen genomes (hence the name genome-derived, epitope driven vaccines or GD-ED). At the core of rapid vaccine development is a tool called an “epitope mapping algorithm”. These tools are deployed in conjunction with other vaccine design tools that concatenate the epitopes into a single delivery vehicle, which, when combined with adjuvant, can be tested in (humanized) animal challenge models. The process from ‘gene to vaccine’ can be as rapid as just a few weeks. Tools for carrying out the task are already available and have been deployed for SARS, H1N1, and a number of other emergent infections (WNV),.

In fact, evidence from animal studies suggests that the number of epitopes required for full protection is a small and definable subset. Careful selection of promiscuous Class II (T helper) epitopes and Class I (Cytotoxic T cell) supertype epitopes can provide greater than 99% coverage of human populations. An effective GD-ED vaccine for humans may need to include at least 50 Class I and Class II broadly HLA-restricted (promiscuous) epitopes that induce multi-functional T cell responses in human PBMC.

Careful selection of vaccine delivery vehicle, route and formulation will improve immunogenicity and may also improve the likelihood of successful protection against disease, and the whole process can be accomplished in months, not years.

Faster, safer route to vaccines for all U.S. citizensHigher-quality, validated vaccine design tools, such as the ones developed by EpiVax over the past 10 years, enable the effective selection of highly immunogenic, vaccine epitopes. The delivery of these epitopes by the right route, in properly designed constructs and effective delivery vehicles, with the right adjuvant is likely to improve immunome-derived epitope-driven vaccine success and lead to significant improvement in the prevention of pandemic spread and improved bioterror preparedness for future generations.

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