The invention relates to chimeric Plasmodium antigenic polypeptides derived from pre-erythrocytic (PE) antigens and associated in a fusion polypeptide. In particular, the invention relates to antigenic fusion polypeptides of malaria parasites wherein said antigenic polypeptides exhibit a protective effect, especially that of eliciting a protective immune response in a host against challenge by Plasmodium sporozoites or a sterile response. Such identified antigenic fusion polypeptides may thus constitute active ingredients suitable for the design of a vaccine candidate, in particular a vaccine suitable for a human host.

Materials and methods useful for generating highly mannosylated pseudotyped lentiviral vector particles comprising a Vpx protein are provided.

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.

In one aspect, the present invention provides recombinant polynucleotides. In some embodiments, the recombinant polynucleotides comprise a cytomegalovirus (CMV) genome, or a portion thereof, and a nucleic acid sequence encoding an antigen, wherein the CMV genome or portion thereof comprises a mutation within a interleukin-10-like gene sequence. Methods for preventing and treating diseases such as infectious diseases and cancer are also provided herein.

The present invention relates, in general, to an immunogen and, in particular, to an immunogen for inducing antibodies that neutralizes a wide spectrum of HIV primary isolates and/or to an immunogen that induces a T cell immune response. The invention also relates to a method of inducing anti-HIV antibodies, and/or to a method of inducing a T cell immune response, using such an immunogen. The invention further relates to nucleic acid sequences encoding the present immunogens.

Methods of reducing the likelihood of a cancer or precancer developing resistance to a cancer therapeutic or prevention agent are provided herein. The methods include administering a vaccine comprising a polynucleotide encoding a polypeptide whose expression or activation is correlated with development of resistance of the cancer or precancer to the cancer therapeutic or prevention agent to a subject. The vaccine may include a polynucleotide encoding a HER2 polypeptide or a truncation, deletion or substitution mutant thereof. Methods of using the vaccine including the polynucleotide encoding the HER2 polypeptide to treat a cancer or precancer are also provided. The vaccines may be administered with a cancer therapeutic or prevention agent or a checkpoint inhibitor immunomodulatory agent.

Methods of reducing the likelihood of a cancer or precancer developing resistance to a cancer therapeutic or prevention agent are provided herein. The methods include administering the cancer therapeutic or prevention agent and a vaccine comprising a polynucleotide encoding a polypeptide whose expression or activation is correlated with development of resistance of the cancer or precancer to the cancer therapeutic or prevention agent to a subject. The vaccine may include a polynucleotide encoding an ESR1 polypeptide or a truncation, deletion or substitution mutant thereof. Methods of using the vaccine including the polynucleotide encoding the ESR1 polypeptide to treat a cancer or precancer are also provided.

Persistence of HIV in anatomic sanctuary sites such as the brain prevents viral eradication. Although combination antiretroviral therapy (cART) inhibits viral replication to undetectable level by standard clinical assay, it does not selectively eliminate virus reservoirs. To target HIV reservoirs, the present inventor developed an HIV Rev-dependent lentiviral vector carrying a series of therapeutic genes, such as diphtheria toxin, anthrolysin O from Bacillus anthracis, human TRAF6, or the herpes simplex 1 virus thymidine kinase gene (HSV-tk). The present disclosure provides the Rev-dependent vectors for targeting viral reservoir in a SIV/rhesus macaque model. SIV-infected rhesus macaques were first treated with cART for over 6 months starting 12 weeks post infection, followed by injections with viral particles assembled from a SIV Rev-dependent vector carrying HSV-tk. Following particle injection, animals were further treated briefly (two weeks) with ganciclovir (GCV), which induces the killing of SIV+, HSV-tk expressing cells. cART was terminated following the GCV treatment, and there was observed a partial control of viral rebound over a period of 4 months after cART cessation. The animal was further treated with additional Rev-dependent vector particles, and viral load was diminished to the undetectable level for over 1 year in the absence of any treatment. These results suggest that the Rev-dependent vector, with or without a functional gene, has the potential to diminish viral reservoirs in vivo and can offer a cure of functional cure of HIV/SIV infection.

Provided herein are methods for treating a patient with human immunodeficiency virus (HIV), comprising administering cellular compositions comprising recombinant allogeneic cells, such as CD4+ T cells. The present invention further relates to compositions and methods for making an allogeneic T-cell-based protective HIV vaccine that induces both cellular and humoral immunity. Related compositions and methods for modulating the immune system using such recombinant cells are also provided.

Provided are HIV-1 fusion polypeptides, polynucleotides encoding such fusion polypeptides, vectors expressing such fusion polypeptides for use in eliciting an immune response against HIV-1; pharmaceutical and immunogenic compositions and kits comprising such fusion polypeptides, polynucleotides or vectors, and methods of use in treating and/or preventing HIV-1. Further provided are methods for design of antiviral vaccines, including vaccines to elicit an immune response against HIV-1.