The present disclosure relates generally to the field of molecular virology, and particularly relates to nucleic acid molecules encoding a modified alphavirus virus viral genome or self-replicating RNA (srRNA) construct, recombinant cells and pharmaceutical compositions containing the same, as well as the use of such nucleic acid molecules, recombinant cells and compositions for production of desired products in cell cultures or in a living body. Also provided are methods for eliciting an immune response in a subject in need thereof, as well as methods for preventing and/or treating rabies virus infection.

The invention features modified alphavirus or flavivirus virus-like particles (VLPs). The invention provides methods, compositions, and kits featuring the modified VLPs. The invention also features methods for enhancing production of modified VLPs for use in the prevention or treatment of alphavirus and flavivirus-mediated diseases. The invention also provides methods for delivering agents to a cell using the modified VLPs.

Provided herein are polypeptides, polynucleotides, expression vectors, infectious clones, virus particles and immunogenic compositions of recombinant alphaviruses which can be used as vaccines. Also provided are methods for eliciting an immune response against alphavirus infection using the immunogenic composition comprising the alphavirus mutants described herein.

Described is a targeting construct encoding a modified Sindbis virus envelope protein, comprising mutations in the E1, E2 and/or E3 proteins, fused with a monomeric biotin-binding molecule. Lentiviral vectors pseudotyped with the novel envelope proteins, such as E2 71 eMA and E2 71 mSAH, can be conjugated with biotinylated targeting ligands The conjugated ligands mediate specific binding and transduction of the target cell types. This lentiviral transduction system can be used to selectively deliver transgenes into specific cell types in vivo, which increases the numbers of vectors reaching the targeted cells and tissues and decreases adverse effects in non-targeted cells and tissues. The vectors transduce B cells without conjugation of targeting ligands. The B cell type most efficiently transduced in this manner is long-lived plasma cells, and thus can be used for long-term transgene expression.

The present invention relates to a process for producing an immunogenic live attenuated Chikungunya virus, as well as pharmaceutical compositions comprising the same.

Disclosed herein are methods for inducing immunity against a severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV2) in a patient in need thereof. The method comprises administering a vaccine composition comprising a self-adjuvanted SARS-CoV2 Spike (S) RNA-based vaccine (AAHI-SC2), followed by administering a replication defective adenovirus (hAd5) vaccine composition, wherein the adenovirus comprises an E1 gene region deletion and an E2b gene region deletion.

Provided is an alphavirus replicon particle (ARP), which comprises (i) alphavirus structural proteins comprising capsid and/or envelope, and (ii) an alphavirus replicon comprising a polynucleotide encoding alphavirus non-structural proteins nsp1, nsp2, nsp3 and nsp4 and at least one gene of interest wherein at least one of capsid, and E3 and E2 in the envelope comprise one or more amino acid alteration but E1 in the envelope comprises no amino acid alteration.

This disclosure provides modified recombinant retroviruses comprisings a transgene encoding a protein with a heterologous secretion signal, containing a 2A-peptide or peptide-like coding sequence operably linked to a heterologous polynucleotide, The disclosure further relates to cells and vector expressing or comprising such vectors and methods of using such modified vectors in the treatment of disease and disorders.

The invention features modified alphavirus or flavivirus virus-like particles (VLPs). The invention provides methods, compositions, and kits featuring the modified VLPs. The invention also features methods for enhancing production of modified VLPs for use in the prevention or treatment of alphavirus and flavivirus-mediated diseases. The invention also provides methods for delivering agents to a cell using the modified VLPs.

The present invention relates to a process for producing an immunogenic live attenuated Chikungunya virus, as well as pharmaceutical compositions comprising the same.