Dengue virus (DENV) represents an emerging/re-emerging infectious disease that causes significant human morbidity and mortality. It is estimated that there are 25 to 100 million cases of DENV infection each year and 2.5 billion people are at risk. Children and infants in endemic countries account for the majority of the 25,000 DENV-associated deaths that occur annually. There is currently no commercial vaccine available. We have developed an innovative vaccine platform that has shown in vivo efficacy against lethal flavivirus infection in two independent models (West Nile virus and Yellow Fever virus) and in this application we will expand on this foundation to develop and produce a new tetravalent vaccine against DENV. The critical obstacle faced by current approaches to live attenuated DENV vaccine development is viral interference, a phenomenon in which the host preferentially mounts an immune response to one or two (but not all) of the four DENV serotypes, leaving the vaccinated subject either unprotected or at potentially increased risk for severe disease if exposed to the wrong DENV serotype. To resolve this problem, our approach utilizes previously attenuated DENV vaccine strains (shown to be safe in human subjects) followed by inactivation with our proprietary hydrogen peroxide (H2O2)-based vaccine technology to prepare highly immunogenic formulations with the potential to elicit a balanced immune response to all four DENV serotypes. This vaccine project encompasses many of the key product development goals listed in RFA-AI-11-014 including, lead vaccine candidate optimization;evaluation of safety, toxicity, and immunogenicity;evaluation of efficacy in appropriate challenge models;evaluation of stability at optimal and elevated storage temperatures;and cGMP manufacturing of vaccine material suitable for completing all applicable IND-enabling preclinical studies. The successful completion of these objectives will result in cGMP-grade vaccine material suitable for future initiation of a Phase I clinical trial, a crucial milestone in the advancement of a human vaccine for this important NIAID Category A Priority Pathogen.

Public Health Relevance

In this application, we provide preliminary data demonstrating the antigenicity, immunogenicity, and protective efficacy of a proprietary new H2O2-based vaccine platform that can be used to develop a safe and effective tetravalent dengue virus vaccine.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-RGK-M (J2))
Program Officer
Cassetti, Cristina
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Oregon Health and Science University
Schools of Medicine
United States
Zip Code
Amanna, Ian J; Slifka, Mark K (2018) Successful Vaccines. Curr Top Microbiol Immunol :
Amanna, Ian J; Slifka, Mark K (2016) Questions regarding the safety and duration of immunity following live yellow fever vaccination. Expert Rev Vaccines 15:1519-1533
Hammarlund, Erika; Thomas, Archana; Poore, Elizabeth A et al. (2016) Durability of Vaccine-Induced Immunity Against Tetanus and Diphtheria Toxins: A Cross-sectional Analysis. Clin Infect Dis 62:1111-1118
Diamond, Michael S; Pierson, Theodore C (2015) Molecular Insight into Dengue Virus Pathogenesis and Its Implications for Disease Control. Cell 162:488-92
Austin, S Kyle; Dowd, Kimberly A (2014) B cell response and mechanisms of antibody protection to West Nile virus. Viruses 6:1015-36
Amanna, Ian J; Slifka, Mark K (2014) Current trends in West Nile virus vaccine development. Expert Rev Vaccines 13:589-608
Slifka, Mark K (2014) Vaccine-mediated immunity against dengue and the potential for long-term protection against disease. Front Immunol 5:195
Slifka, Mark K; Amanna, Ian (2014) How advances in immunology provide insight into improving vaccine efficacy. Vaccine 32:2948-57
Pinto, Amelia K; Richner, Justin M; Poore, Elizabeth A et al. (2013) A hydrogen peroxide-inactivated virus vaccine elicits humoral and cellular immunity and protects against lethal West Nile virus infection in aged mice. J Virol 87:1926-36
Rowe, Alexander M; Murray, Susan E; Raue, Hans-Peter et al. (2013) A cell-intrinsic requirement for NF-*B-inducing kinase in CD4 and CD8 T cell memory. J Immunol 191:3663-72

Showing the most recent 10 out of 11 publications