The present disclosure generally relates to genetic methods of manipulating helminths, e.g., hookworms, to act as a biological delivery vehicle for therapeutic polypeptides in mammals. Furthermore, the disclosure is drawn to compositions comprising genetically modified hookworms and methods of use, including the administration of the helminths to one or more mammals to provide a continuous supply of a synthetic or modified polypeptide (e.g., HIV neutralizing antibodies) which may mitigate infection and/or infection intensity, otherwise resulting in an increase in a desirable phenotypic trait.

The present invention provides highly efficient methods, and compositions related thereto, for generating high titer human antibodies or antibody fragments thereof in a mammalian subject. The methods comprise administering a virus or virus-like particle to a mammal comprising heterologous immune cells and isolating a population of immunoglobulin-producing cells from the mammal, thereby producing the antibodies or antibody fragments thereof.

A method of inactivating a proviral DNA integrated into the genome of a host cell latently infected with a retrovirus by treating the host cell with a composition comprising a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease, and two or more different guide RNAs (gRNAs), wherein each of the at least two gRNAs is complementary to a different target nucleic acid sequence in a long terminal repeat (LTR) in the proviral DNA, and inactivating the proviral DNA. A composition for use in inactivating a proviral DNA integrated into the genome of a host cell latently infected with a retrovirus including isolated nucleic acid sequences comprising a CRISPR-associated endonuclease and a guide RNA, wherein the guide RNA is complementary to a target sequence in a human immunodeficiency virus.

Disclosed are compositions and methods related to replication deficient Sindbis viruses that are able to function as controls for nucleic acid diagnostic assays (e.g., nucleic acid sequencing based assays and/or nucleic acid amplification based assays).

The present invention utilizes a Cas9 nickase which nicks a flanking target sequence to a duplicated gene sequence (e.g., a retroviral LTR). This nicking causes a genomic collapse of the sequence between the nick and the LTR, thereby deleting the sequence from the genome. Because the nickase does not introduce mutations at the target site, this method can be repeated maximize the efficiency (e.g., 100% of retroviral genome excision. For example, this method is useful to delete all PERVs within a pig genome intended for human transplantation. Further, such PERV-free cells can then be used to clone PERV-free pigs. Furthermore, this method is useful to remove amplified gene repeats in cancer cells.

The invention relates to a process for producing enveloped viruses in a mildly acid medium. The processes of the invention are useful for producing and recovering at a large scale enveloped viruses under conditions observing good manufacturing practice (GMP).

It is disclosed herein that viruses coated in silica retain infectivity and the capacity to induce an immune response in an infected host. In addition, silicified virus is remarkably resistant to desiccation. Provided herein are methods of inducing a virus-specific immune response in a subject by administering to the subject an effective amount of silicified virus or silicified virus particles. Methods of enhancing a virus-specific cell-mediated immune response (such as a T cell-mediated immune response) in a subject by administering to the subject a silicified virus or silicified virus particles are also described herein. Further provided are immunogenic compositions comprising silicified virus or silicified virus particles, such as compositions useful as vaccines. The immunogenic compositions include a pharmaceutically acceptable carrier and/or an adjuvant.

The present disclosure provides compositions (i.e., amplification primers and probes), methods, and kits that are particularly useful for detecting and/or quantifying nucleic acids present in a sample, such as those derived from HIV or a lentiviral vector.

Methods for inducing an immune response against Human Immunodeficiency Virus (HIV) in HIV-infected subjects undergoing antiretroviral therapy (ART) are described. The methods include administering an adenovirus vector primer vaccine and a modified vaccinia virus (MVA) vector booster vaccine encoding mosaic HIV antigens.

The invention relates to peptides comprising part or all of a conserved element within a Center-of-Tree (COT) sequence derived from a family of polypeptides encoded by naturally occurring variants of HIV. The invention also relates to immunogenic compositions and vaccines comprising said peptides. The invention also relates to methods for the identification of HIV controller patients based on the detection of the T cells of the patient to mount a cytotoxic T cell response against said peptides and to methods for the identification of immunogenic peptides within a family of variant polypeptides.