The present disclosure relates to the production of transmissible vims defective interfering particles (DIPs), particularly those of dengue virus as well as methods of their production. The DIPs have particular utility as immunogenic compositions and vaccines.

The disclosure provides compositions and methods involving viral RNA segments for use in modulating immune responses, including inhibition inflammation related to pathogenic T-cell activation. In addition, modification of the viral sequences responsible for modulating immune response provides for improved vaccine formulations.

Aspects of the disclosure relate to nucleic acid vaccines. The vaccines include one or more RNA polynucleotides having an open reading frame encoding one or more Chikungunya antigen(s), one or more Zika virus antigens, and one or more Dengue antigens. Methods for preparing and using such vaccines are also described.

Provided is a method of inhibiting viral replication, including contacting one or more cells that has been infected or contacted with a flavivirus with an effective amount of niclosamide, temoporfin, nitazoxanide, tizoxanide, erythrosin B, methylene blue. Contacting one or more cells that have been infected with a flavivirus may include administering the compound to a mammal, a human, or other subject. The flavivirus may be Dengue virus serotype 1, Dengue virus serotype 2, Dengue virus serotype 3, Dengue virus serotype 4, yellow fever virus, West Nile virus, Zika virus, Japanese encephalitis virus, tick-born encephalitis virus, Powassan virus, St. Louis encephalitis virus, or other flavivirus.

Provided is a method of inhibiting viral replication, including contacting one or more cells that has been infected or contacted with a flavivirus with an effective amount of niclosamide, temoporfin, nitazoxanide, tizoxanide, erythrosin B, methylene blue. Contacting one or more cells that have been infected with a flavivirus may include administering the compound to a mammal, a human, or other subject. The flavivirus may be Dengue virus serotype 1, Dengue virus serotype 2, Dengue virus serotype 3, Dengue virus serotype 4, yellow fever virus, West Nile virus, Zika virus, Japanese encephalitis virus, tick-born encephalitis virus, Powassan virus, St. Louis encephalitis virus, or other flavivirus.

Certain embodiments of the invention include methods and compositions for evaluating flaviviruses, such as Zika virus, for the purpose of identifying, typing, and/or categorizing/speciation of virus in samples using nucleic acid sequencing.

Certain embodiments of the invention include methods and compositions for evaluating flaviviruses, such as Zika virus, for the purpose of identifying, typing, and/or categorizing/speciation of virus in samples using nucleic acid sequencing.

Disclosed herein is a composition including a recombinant nucleic acid sequence that encodes an antibody. Also disclosed herein is a method of generating a synthetic antibody in a subject by administering the composition to the subject. The disclosure also provides a method of preventing and/or treating disease in a subject using said composition and method of generation.

Aspects of the disclosure relate to nucleic acid vaccines. The vaccines include one or more RNA polynucleotides having an open reading frame encoding one or more Chikungunya antigen(s), one or more Zika virus antigens, and one or more Dengue antigens. Methods for preparing and using such vaccines are also described.

Dengue Fever (DF) and Dengue Hemorrhagic Fever (DHF) are significant global public health problems and understanding the overall immune response to infection will contribute to appropriate management of the disease and its potentially severe complications. Live attenuated and subunit vaccine candidates, which are under clinical evaluation, induce primarily an antibody response to the virus and minimal cross-reactive T cell responses. Currently, there are no available tools to assess protective T cell responses during infection or post vaccination. Herein, we report novel, naturally processed and presented MHC class I restricted epitopes, a subset of which binds to and activates T cells in both an HLA-A2 and HLA-A24 restricted manner. We show that epitope specific T cells can be activated in vivo in transgenic mice and in vitro in seropositive and seronegative individuals and that these T cells are functional, recognizing peptide pulsed and dengue virus infected cells in a pro-inflammatory and cytotoxic manner. These epitopes have potential as new informational and diagnostic tools to characterize T cell immunity in Dengue virus (DV) infection, and may serve as a universal vaccine candidate complementary to current vaccines in trial.