Dengue virus (DENV) is a flavivirus that infects 100 million people and causes severe disease in ~500,000 people annually. DENV nonstructural protein 1 (NS1) is secreted by infected cells and found at high levels in patient sera during the acute illness. To investigate the potential for NS1 as a vaccine candidate, we examined the protective efficacy of immunization with recombinant NS1 protein against lethal DENV infection in a mouse model. Interferon α/β receptor-deficient mice were injected intraperitoneally 3 times over an 8-week period with 20 ug recombinant NS1 with different adjuvants, including alum, Sigma adjuvant system (SAS), CpG DNA, MF59 and/or monophosphoryl lipid A (MPLA). Two weeks after the third immunization, vaccinated mice were infected with a lethal dose of DENV2. Vaccination with NS1 combined with SAS and CpG DNA provided complete protection against mortality along with reduced morbidity whereas mice immunized with NS1 combined with alum and/or CpG DNA displayed little or no protection against DENV2 challenge. All vaccination groups demonstrated comparable levels of total anti-NS1 IgG; however, mice immunized with SAS+CpG had higher levels of anti-NS1 IgG2b as compared to alum (p=0.057). Data comparing mice immunized with NS1 together with MPLA and MF59 will also be presented. Thus, immune responses to a DENV nonstructural protein can provide protection against severe disease and NS1 may provide an alternative vaccine against dengue.
- Copyright © 2013 by The American Association of Immunologists, Inc.