The invention features stabilized human immunodeficiency virus (HIV) envelope (Env) trimers. The invention also features vaccines, nucleic acids, and vectors to deliver and/or facilitate production of the stabilized HIV Env trimers. In addition, the invention features methods of making and using the stabilized HIV Env trimers of the invention.

Compositions and vaccine combinations containing synthetic HIV envelope proteins, and methods for inducing an immune response against human immunodeficiency virus (HIV) infection are described. Viral expression vectors encoding the synthetic HIV envelope proteins can be used in the vaccine combinations to induce immune responses against HIV and provide improved protective immunity against HIV.

The invention provides compositions and methods to induce and boost antibody response, including but not limited to IgG responses binding to HIV-1 in a subject in need thereof, wherein the induced/boosted plasma level of the antibody responses, for example V3 and/or CD4 binding site antibody responses, is over a threshold level and is associated with reduced risk of maternal-to-child-transmission (MTCT) of HIV-1.

The present invention provides novel nanoparticle presented vaccine compositions that are stabilized with a locking domain. Various immunogens can be employed in the preparation of the vaccine compositions, including viral immunogens such as HIV-1 and Ebola viral immunogens, and non-viral immunogens such as immunogens derived from bacteria, parasites and mammalian species. The invention also provides methods of using such vaccine compositions in various therapeutic applications, e.g., for preventing or treating viral infections.

This disclosure relates to the genetic modification of DNMT3A gene in immune cells. In certain embodiments, the modified immune cells may be used in adoptive T cells therapies to enhance immune responses against cancer or chronic infections. In certain embodiments, the disclosure relates to deleting, changing, or inserting nucleotides within the DNMT3A gene in immune cells, e.g., human CD8 T cells, such that the DNMT3A gene product does not function for methylation. In certain embodiments, modification of the DNMT3A gene provides an improvement in antigen-specific T cells functions and/or an enhancement of the longevity of the cells.

The present invention relates to bispecific molecules that are capable of localizing an immune effector cell that expresses an activating receptor to a virally infected cell, so as to thereby facilitate the killing of the virally infected cell. In a preferred embodiment, such localization is accomplished using bispecific molecules that are immunoreactive with an activating receptor of an immune effector cell and to an antigen expressed by a cell infected with a virus wherein the antigen is detectably present on the cell infected with the virus at a level that is greater than the level at which the antigen is detected on the virus by the bispecific molecules, and to the use of such bispecific molecules in the treatment of latent viral infections.

This invention relates to novel anti-HIV antibodies that can be used in the treatment and detection of human immunodeficiency virus (HIV). These antibodies exhibit a high degree of sensitivity and can provide a broad range of specificity.

The invention provides a method for obtaining a broadly neutralizing antibody (bNab), including screening memory B cell cultures from a donor PBMC sample for neutralization activity against a plurality of HIV-1 species, cloning a memory B cell that exhibits broad neutralization activity; and rescuing a monoclonal antibody from that memory B cell culture. The resultant monoclonal antibodies may be characterized by their ability to selectively bind epitopes from the Env proteins in native or monomeric form, as well as to inhibit infection of HIV-1 species from a plurality of clades. Compositions containing human monoclonal anti-HIV antibodies used for prophylaxis, diagnosis and treatment of HIV infection are provided. Methods for generating such antibodies by immunization using epitopes from conserved regions within the variable loops of gp120 are provided. Immunogens for generating anti-HIV1 bNAbs are also provided. Furthermore, methods for vaccination using suitable epitopes are provided.

Disclosed herein is a composition including a recombinant nucleic acid sequence that encodes an antibody to an HIV antigen. 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 an HIV infection in a subject using said composition and method of generation.

Disclosed are nucleic acid sequences comprising a modified HIV Gag sequence, wherein the modified HIV Gag sequence comprises, from 5′ to 3′, a matrix domain (MA), capsid (CA) domain, SP1 region, nucleocapsid (NC) domain, SP2 region, and p6 domain, wherein the modified HIV Gag sequence further comprises an exogenous sequence of interest between the NC domain and the SP2 region. Disclosed are methods of producing a recombinant lentivirus comprising transfecting a cell with a plasmid comprising the nucleic acid sequence of one or more of the disclosed nucleic acid sequences in combination with an envelope plasmid. Disclosed are methods of monitoring lentivirus assembly, budding, and/or maturation comprising transfecting a cell with a plasmid comprising any one of the disclosed nucleic acid sequences in combination with an envelope plasmid, wherein the exogenous sequence of interest encodes a detection agent. Disclosed are methods of treating a subject with a therapeutic agent comprising administering to a subject in need thereof a recombinant lentivirus, wherein the recombinant lentivirus comprises one or more of the disclosed nucleic acid sequences, wherein the exogenous sequence of interest encodes a therapeutic agent.