The present invention discloses a method and its variations for simultaneous detection of antibodies against two or more antigens of human immunodeficiency virus (HIV) and determination of approximate time (duration) post HIV infection, thereby confirming the infection, and determination of recency of an HIV infection. The number of individuals with recently infected HIV in a given period may be further used to estimate incidence of HIV in a population.

This disclosure relates to methods of promoting immune responses against HIV and compositions related thereto. In certain embodiments, this disclosure relates to methods of vaccinating for HIV comprising administering to the subject a priming composition followed by a boosting composition. In certain embodiments, the priming composition comprises a recombinant virus such as recombinant MVA that encodes an Env protein of HIV or segment thereof. In certain embodiments, the boosting composition comprises a trimeric cyclically permuted gp120 chimeric protein reported herein or DNA encoding the same.

The present invention discloses immunogenic compositions including recombinant peptides and proteins comprising human immunodeficiency viruses (HIV) antigens and immunogens, e.g., gp 120 protein peptides. In some aspects, the immunogenic composition comprises a secreted fusion protein comprising a soluble HIV viral antigen joined by in-frame fusion to a C-terminal portion of a collagen which is capable of self-trimerization to form a disulfide bond-linked trimeric fusion protein. In some aspects, the immunogenic compositions provided herein are useful for generating an immune response, e.g., for treating or preventing an HIV infection. In some aspects, the immunogenic compositions provided herein may be used in a vaccine composition, e.g., as part of a prophylactic and/or therapeutic vaccine. Also provided herein are methods for producing the recombinant peptides and proteins, prophylactic, therapeutic, and/or diagnostic methods, and related kits.

The present disclosure relates to genetically modified T cells comprising a transgene encoding an engineered antigen specific receptor, wherein expression of an endogenous gene selected from MNK1, MNK2, or both are inhibited in the genetically modified T cell in order to enhance central memory T cell subsets in cellular immunotherapy compositions.

Disclosed are methods of a method of making a nanostructure, comprising adding a component A (compA) protein to a solution comprising a component B (compB) protein under conditions that minimize shear stress, thereby forming a compA:compB complex. Further disclosed are methods of making a nanostructure, comprising (i) providing a first inlet fluid stream comprising a first protein and a second inlet fluid stream comprising a second protein, and (ii) contacting the first inlet fluid stream and the second inlet fluid stream to form an outlet stream, wherein mixing of the first protein and the second protein occurs in the outlet stream, thereby forming a protein complex comprises the first protein and the second protein. A microfluidic mixer may be used. The methods may further comprise purifying the compA:compB complex from excess compA, excess compB, and/or other impurities by filtering the solution with a 1,000 kDa membrane or an equivalent thereof.

Disclosed are methods of a method of making a nanostructure, comprising adding a component A (compA) protein to a solution comprising a component B (compB) protein under conditions that minimize shear stress, thereby forming a compA:compB complex. Further disclosed are methods of making a nanostructure, comprising (i) providing a first inlet fluid stream comprising a first protein and a second inlet fluid stream comprising a second protein, and (ii) contacting the first inlet fluid stream and the second inlet fluid stream to form an outlet stream, wherein mixing of the first protein and the second protein occurs in the outlet stream, thereby forming a protein complex comprises the first protein and the second protein. A microfluidic mixer may be used. The methods may further comprise purifying the compA:compB complex from excess compA, excess compB, and/or other impurities by filtering the solution with a 1,000 kDa membrane or an equivalent thereof.

The invention relates to PGT121-germline-targeting designs, trimer stabilization designs, combinations of those two, trimers designed with modified surfaces helpful for immunization regimens, other trimer modifications and on development of trimer nanoparticles and methods of making and using the same.

Fc-fusion protein derivatives against HIV have enhanced yield in mammalian cells, and extended antiviral and immunomodulatory activities. The Fc-fusion protein derivatives can block the entry of human immunodeficiency virus (HIV) into host cells, elicit effector functions through the activation of natural killer (NK) and other immune system cells, can be produced with high yield in mammalian cells, and have extended activity in vivo. Nucleic acids, vectors and host cells can express the Fc-fusion protein derivatives, which have therapeutic and diagnostic applications in human health.

Human cytomegalovirus vectors comprising heterologous antigens are disclosed. The vectors derived from the TR strain, are ganciclovir sensitive, include active US2, US3, US6, US7 and UL131A genes, and have a deleterious or inactivating mutation in the UL82 gene preventing the expression of pp71.

Provided are methods of detecting replication competent virus, e.g., replication competent retrovirus such as gammaretrovirus or lentivirus, in a sample containing a cell transduced with a viral vector particle encoding a recombinant and or heterologous molecule, e.g., heterologous gene product. The methods may include assessing transcription of one or more target genes, such as viral genes, that are expressed in a retrovirus but not expressed in the viral vector particle. Replication competent retrovirus may be determined to be present if the levels of RNA of the one or more target genes is higher than a reference value, which can be measured directly or indirectly, including from a positive control sample containing RNA from the respective target gene at a known level and/or at or above the limit of detection of the assay.