Working together to develop new and more effective vaccines

May 26, 2011

Indicated disease(s) : Viral Infections

Technology title : E6020 – Development of a Synthetic Toll-like receptor (TLR) 4 Agonist for use as a Vaccine Adjuvant


Vaccines have been one of the great public health successes, representing a practical, low-cost, and highly effective method to eradicate or at least short-circuit the spread of infectious disease. Vaccines are responsible for the control of many infectious diseases that were once common including small pox, polio, measles, diphtheria, pertussis (whooping cough), rubella (German measles), mumps, tetanus, and Haemophilus influenzae type b (Hib). Although the administration of antigen to establish immune memory and subsequent rapid response to infection is conceptually simple, we find ourselves increasingly challenged in developing effective vaccines to meet the world's current needs. Malaria, HIV, and evolving strains of influenza, among other infectious diseases affecting millions of people in the world remain challenges.

Determining an appropriate antigen is critical, but once this choice is made vaccine developers have found themselves limited in the options available in adjuvants and delivery technologies. Although research in these areas is advancing rapidly there is a lack of approved molecules that safely and effectively enhance anti-vaccine responses in humans, particularly when cytolytic cellular responses are desired. The use of TLR ligands to boost vaccine performance is being thoroughly explored with some success that has led to the commercialization of a few vaccine products in the US and Europe.

Technology development

E6020 is a totally synthetic and selective TLR4 agonist whose structure is based on the structure and physicochemical properties of the natural TLR4 agonist E. coli lipid A. E6020 was found to show selective but attenuated TLR4 agonism and demonstrated the potential of enhancing the immune response to various vaccine antigens in mice. Importantly, the agonist enhances IgG2a, which in mice is associated with Th1 activation. Correspondingly, the titer of antigen-specific IgE is decreased.

Thus, addition of the adjuvant to traditional vaccine formulations might enhance Th1 or γ-interferon responses and modulate allergenicity in the clinic. The adjuvant used alone at low doses appears to generate a balanced Th1/Th2 response, rather than skewing to either extreme 1-6).

E6020 was selected as a candidate for development with recommendation that it be developed as a nonexclusive licensing program with support from Eisai's business development team. Currently it is at the preclinical stage of development to obtain nonexclusive licenses with companies who have expertise in vaccine development.

Sanofi-Pasteur and Eisai signed an option agreement to a nonexclusive license to use E6020 in vaccine programs toward various infectious diseases. These companies would use E6020 as an adjuvant in their vaccine formulation and advance the technology into the clinic followed by commercialization. Eisai will manufacture and supply cGMP E6020 throughout these developments. The analytical, physical chemical, ADME and toxicological data required for clinical development and beyond have been obtained or will be provided by Eisai. Currently, Eisai has ample quantities cGMP E6020 for Phase I and II clinical studies. Phase III, cGMP E6020 material production will be produced once requested.

Selected References

  • 1)
    Ishizaka, Sally T. et al. Expert Review of Vaccines (2007), 6(5), 773-784.
  • 2)
    Baudner, Barbara C. et al. Pharmaceutical Research (2009), 26(6), 1477-1485.
  • 3)
    Morefield, Garry L. et al. Clinical and Vaccine Immunology (2007), 14(11), 1499-1504.
  • 4)
    Przetak, Melinda. et al. Vaccine (2003), 21(9-10), 961-970.
  • 5)
    Seydel, Ulrich. et al. European Journal of Immunology (2003), 33(6), 1586-1592.
  • 6)
    Hawkins, Lynn D. et al. Journal of Pharmacology and Experimental Therapeutics (2002), 300(2), 655-661.


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