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.

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.

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

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.

This disclosure provides replication-incompetent adenoviral vectors useful in vaccine development and gene therapy. The disclosed vectors comprise a selective deletion of E3 and are particularly useful for preparation of vaccines development and for gene therapy using toxic transgene products that result in vector instability that occurs when the entire E3 domain is deleted.

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.

The present disclosure provides materials and methods related to engineered bacteria for use in vaccines. In particular, the present disclosure provides novel compositions and methods for generating vaccine compositions comprising bacteria (e.g., Lactobacillus) engineered to express immunogenic polypeptides and immunogenicity-enhancing adjuvant polypeptides to treat and/or prevent infection from a pathogenic organism (e.g., coronavirus).

Polyvalent, primary isolate nucleic acid compositions for inducing an immune response against HIV are disclosed. The compositions and methods described herein are for the use of a nucleic acid composition that encodes one or more different HIV envelope glycoproteins. The synthetic, codon-optimized DNAs encoding one or more HIV proteins are a combination of different nucleic acids, such as DNA plasmids, generated from primary isolate DNA of different HIV major group genetic clades and/or different proteins. HIV polypeptide compositions for inducing an immune response against HIV are also disclosed. Methods for using the polypeptide compositions before, at the same time as, and/or after administration of the DNA compositions are provided.

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.