The present disclosure relates to a method for constructing a producer cell and the producer cell obtained by the method, wherein the producer cell is for producing a retroviral vector carrying a nucleic acid fragment of interest.

The present invention provides new stable packaging cell lines and producer cell lines as well as methods to obtain them, and a new method to produce lentiviral vectors using such cell lines. New methods and packaging cell lines of the invention are generated using a baculo-AAV hybrid system for stable expression of structural and regulatory lentiviral proteins, such system comprising a baculoviral backbone containing an integration cassette flanked by AAV ITR, in combination with a plasmid encoding rep protein. This system allows to obtain a stable integration of the structural and regulatory HIV-1 proteins gag/pol and rev. The system allows to obtain a first intermediate including only the structural and regulatory HIV proteins gag/pol and rev, to be used as starting point to obtain stable packaging cell lines as well as producer cell lines.

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 provides broadly neutralizing antibodies against HIV, compositions comprising the same and methods of use thereof.

Described is an engineered viral particle programmed with T cell targeting specificity. The viral particles comprise: at least one viral vector, such as bacteriophage T4; and at least one CD4-binding protein displayed on the surface of the viral vector. Also described is a method of reactivate latent HIV-1 and cure patient with HIV-1 infection, using such an engineered viral particle.

HIV-1 Env ectodomain trimers stabilized in a prefusion mature closed conformation and methods of their use and production are disclosed. In several embodiments, the HIV-1 Env ectodomain trimers and/or nucleic acid molecules can be used to generate an immune response to HIV-1 in a subject. In additional embodiments, the therapeutically effective amount of the HIV-1 Env ectodomain trimers can be administered to a subject in a method of treating or preventing HIV-1 infection.

The present disclosure provides compositions and methods for the generation of an antibody or immunogenic composition, such as a vaccine, through epitope focusing by variable effective antigen surface concentration. Generally, the composition and methods of the disclosure comprise three steps: a “design process” comprising one or more in silico bioinformatics steps to select and generate a library of potential antigens for use in the immunogenic composition; a “formulation process”, comprising in vitro testing of potential antigens, using various biochemical assays, and further combining two or more antigens to generate one or more immunogenic compositions; and an “administering” step, whereby the immunogenic composition is administered to a host animal, immune cell, subject or patient. Further steps may also be included, such as the isolation and production of antibodies raised by host immune response to the immunogenic composition.

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.

A polypeptide mimicking epitope of glycoprotein gp120 of HIV-1 virus that is recognized by a paratope of broadly neutralizing antibody VRC01 and has the length up to 100 amino acid residues and contains an amino acid sequence:

TABLE-US-00001 (SEQ ID NO. 1): X.sup.1YKNX.sup.2INX.sup.3AX.sup.4X.sup.5VX.sup.6X.sup.7VKRX.sup.8IDX.sup.9ILAX.sup.10LP X.sup.1 is selected from amino acids A, N, R; X.sup.2 is selected from amino acids A, R, D; X.sup.3 is selected from amino acids R, V, P; X.sup.4 is selected from amino acids V, L, S; X.sup.5 is selected from amino acids T, G, R; X.sup.6 is selected from amino acids G, T; X.sup.7 is selected from amino acids L, A; X.sup.8 is selected from amino acids V, I; X.sup.9 is selected from amino acids G, A, R; X.sup.10 is selected from amino acids R, A, G;
with a directly attached alpha-helical structure at the N-terminus or C-terminus is disclosed.