Provided is an rtTA and single chain rtTA variants and uses thereof for inducible expression of a nucleic acid of interest. Nucleic acid molecules comprising an improved rtTA and/or sc rtTA sequence according to the invention are also provided, as well as vectors, replicons and cells comprising such nucleic acid molecules.

The present invention is directed to novel promiscuous and artificial T helper cell epitopes (Th epitopes) designed to provide optimum immunogenicity of a target antigenic site. The target antigenic site can include a B cell epitope, a CTL epitope, a peptide hapten, a non-peptide hapten, or any immunologically reactive analogue thereof. The disclosed Th epitopes, when covalently linked to a target antigenic site in a peptide immunogen construct, elicit a strong B cell antibody response or an effector T cell response to the target antigenic site. The Th epitopes are immunosilent on their own, i.e., little, if any, of the antibodies generated by the peptide immunogen constructs will be directed towards the Th epitope, thus allowing a very focused immune response directed to the targeted antigenic site. The promiscuous artificial Th epitopes provide effective and safe peptide immunogens that do not generate inflammatory, anti-self, cell-mediated immune responses following administration.

The present invention relates to a method for transducing a target cell, the method comprising the step of contacting a target cell with a retroviral vector and a compound capable of enhancing transduction efficiency or a combination of such compounds, wherein the target cell is pre- and/or co-stimulated by pre- and/or co-incubation with said transduction enhancing compound or a combination of transduction enhancing compounds prior to and/or during contacting the target cell with the retroviral vector.

Provided herein are HIV-1 vaccines comprising a carrier and a population episensus antigen determined using the EpiGraph approach. Also provided are HIV-1 vaccines comprising a carrier, a population episensus antigen, and a tailored antigen. Also provided are methods of designing and producing an HIV-1 vaccine for a subject comprising designing vaccine antigens to optimally cover the diversity within a geographic area using an antigen amino acid sequence generated using the EpiGraph approach, and producing said designed vaccine antigen. Also provided are methods of inducing an effector memory T cell response comprising designing the one or more EpiGraph amino acid sequences, producing a vaccine comprising the one or more EpiGraph amino acid sequences and a vector, and administering the vaccine to a subject. Further provided are methods of treating HIV-1 in a subject comprising administering an effective amount of the described HIV-1 vaccines to the subject in need thereof.

Methods for inducing an immune response against Human Immunodeficiency Virus (HIV) in HIV-infected subjects undergoing antiretroviral therapy (ART) are described. The methods involve initial administration of an adenovirus vector vaccine and subsequent administration of a poxvirus vector vaccine, followed by administration of anti-HIV broadly neutralizing antibodies (bNAb).

In certain aspects the invention provides HIV-1 immunogens, including HIV-1 envelopes with optimized V2 loop for antibody induction.

Provided is a recombinant BCG employing a pMyong2 vector system to express HIV-1 p24 and a use thereof as a HIV-1 vaccine. rBCG-pMyong2-p24, which is a pMyong2 vector system, was found to induce the upregulation of HIV-1 p24 gag expression in rBCG and infected antigen-presenting cells (APC) and to induce improved p24-specific immune responses in vaccinated mice, compared to rBCG-pAL-p24 in a pAL5000 derived vector system. rBCG-pMyong2-p24 was identified to exhibit a higher p24-specific Ab production level than rSmeg-pMyong2-p24 in the same pMyong2 vector system. Therefore, the recombinant BCG employing rBCG-pMyong2-p24 to express HIV-1 p24 according to the present invention is identified to elicit enhanced immune responses to HIV-1 infection in mouse model systems and thus can be expected to be used as a prime vaccine in the heterologous prime-boost vaccination strategy against HIV-1 infection.

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.

Recombinant antibody-based molecules that trigger both T-cell and B-cell immune responses are disclosed. The recombinant molecules are comprised by at least one targeting unit and at least one antigenic unit connected through a dimerization motif. Also disclosed are nucleic acid molecules encoding the recombinant antibody-based molecule and methods of treating multiple myeloma or lymphoma in a patient using the recombinant antibody-based molecules or the nucleic acid molecules.

Disclosed herein are methods, compositions, and kits useful to enhance an immune response against an antigen and to improve vaccine efficacy. The disclosed methods, compositions, and kits may be utilized to improve vaccine immunogenicity and enhance immune protection following subsequent antigen challenges. In some embodiments, the methods include co-administering a blocker of the IFN-I pathway with an antigen that is used as part of a vaccine, such as a viral vaccine.