Provided herein are, inter alia, methods and compositions for treating and preventing arenavirus infection. Compositions include recombinant arenavirus glycoproteins that are able to form glycoprotein timers. The glycoprotein timers are contemplated to be effective for preventing and/or treating arenavirus infections.

A recombinant attenuated Mopeia virus (MOPV) comprising a recombinant genomic S segment that encodes a nucleoprotein having attenuated exonuclease activity, and optionally further encodes a non-MOPV arenavirus glycoprotein. Use of the recombinant attenuated MOPV to induce an immune response in a subject.

Disclosed herein are methods and exemplary compositions associated with antigen purification, exemplary aspects of which may include harvesting viral and antigenic substances from source organisms; and a purification platform comprising chemical separation and size-difference separation for the removal of contaminants, debris and impurities from the viral and protein (e.g. antigenic, including influenza hemagglutinin antigens) substances, as well as their concentration and collection.

Disclosed herein are methods and exemplary compositions associated with virus purification, antigen purification, and conjugation of virus and proteins (e.g., antigen) to form vaccines for delivery of immunological and other therapeutic agents, exemplary aspects of which may include harvesting viral and antigenic substances from source organisms; a purification platform comprising chemical separation and size-difference separation for the removal of contaminants, debris and impurities from the viral and protein (e.g. antigenic, including influenza hemagglutinin antigens) substances, as well as their concentration and collection; and a conjugation platform providing activation of the virus at a pH that increases binding rate and binding propensity between the virus and the protein, wherein embodiments related to the conjugation platform include controlling the ratio of virus to protein.

The invention relates to an infectious arenavirus particle that is engineered to contain a genome with the ability to amplify and express its genetic information in infected cells but unable to produce further infectious progeny particles in normal, not genetically engineered cells. One or more of the four arenavirus open reading frames glycoprotein (GP), nucleoprotein (NP), matrix protein Z and RNA-dependent RNA polymerase L are removed or mutated to prevent replication in normal cells but still allowing gene expression in arenavirus vector-infected cells, and foreign genes coding for an antigen or other protein of interest or nucleic acids modulating host gene expression are expressed under control of the arenavirus promoters, internal ribosome entry sites or under control of regulatory elements that can be read by the viral RNA-dependent RNA polymerase, cellular RNA polymerase I, RNA polymerase II or RNA polymerase III. The modified arenaviruses are useful as vaccines and therapeutic agents for a variety of diseases.

The present application relates to Pichinde viruses with rearrangements of their open reading frames (“ORF”) in their genomes. In particular. described herein is a modified Pichinde virus genomic segment, wherein the Pichinde virus genomic segment is engineered to carry a viral ORF in a position other than the wild-type position of the ORF. Also described herein are trisegmented Pichinde virus particles comprising one L segment and two S segments or two L segments and one S segment. The Pichinde virus, described herein may be suitable for vaccines md/or treatment of diseases and/or for the use in immunotherapies.

The invention relates to an infectious arenavirus particle that is engineered to contain a genome with the ability to amplify and express its genetic information in infected cells but unable to produce further infectious progeny particles in normal, not genetically engineered cells. One or more of the four arenavirus open reading frames glycoprotein (GP), nucleoprotein (NP), matrix protein Z and RNA-dependent RNA polymerase L are removed or mutated to prevent replication in normal cells but still allowing gene expression in arenavirus vector-infected cells, and foreign genes coding for an antigen or other protein of interest or nucleic acids modulating host gene expression are expressed under control of the arenavirus promoters, internal ribosome entry sites or under control of regulatory elements that can be read by the viral RNA-dependent RNA polymerase, cellular RNA polymerase I, RNA polymerase II or RNA polymerase III. The modified arenaviruses are useful as vaccines and therapeutic agents for a variety of diseases.

The present invention provides methods of preventing, reducing or reversing T cell exhaustion in a patient having a disease. The present invention also provides methods for treating a disease in a patient having the disease. The present invention also provides an engineered T cell, and uses thereof.

The present application provides immunotherapies for Hepatitis B virus infections. Provided herein are genetically modified arenaviral vectors suitable as vaccines for prevention and treatment of Hepatitis B virus infections. Also provided herein are pharmaceutical compositions and methods for the treatment of Hepatitis B virus infections. Specifically, provided herein are pharmaceutical compositions, vaccines, and methods of treating Hepatitis B virus infection.

The present invention is directed to RNA suitable for use in treatment and/or prophylaxis of an infection with Lassa virus (LASV) or of a disorder related to such an infection. The invention further concerns a method of treating or preventing a disorder or a disease, first and second medical uses of the RNA, compositions, and vaccines. Further, the invention is directed to a kit, particularly to a kit of parts, comprising the RNA, compositions and vaccines.