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Abstract
Paramyxoviridae is a family of enveloped viruses in the order Mononegavirales. They have non-segmented, negative-sense, single-stranded RNA genomes and infect most vertebrates. Because they do not have a DNA part to their life cycle, they cannot integrate their genome into a host cell genome. Countless vaccine technologies, including recombinant protein, formaldehyde-inactivated HIV, live attenuated HIV, plasmid DNA, and viral-vectored vaccines, have been explored to develop a human immunodeficiency virus (HIV) vaccine. Despite decades of research, there is no licensed vaccine for HIV. Due to disappointing results with vaccines focusing on generating HIV-specific antibodies, HIV vaccine focus shifted to generating HIV-specific cellular responses. Live, replication-competent viral vectors expressing an antigen can induce robust antigen-specific cellular responses. This work investigates the use of multiple Paramyxovirus vectors, including recombinant Parainfluenza virus 5 (PIV5), recombinant J paramyxovirus (JPV), and PIV5 amplifying virus-like particles (AVLPs), to express HIV immunogens. First, a rJPV-vectored vaccine expressing HIV-env was generated and analyzed. It induced anti-HIV humoral and cellular responses in mice. Second, rPIV5-vectored vaccines expressing mosaic immunogens, tHIVconvX, induced broadly-reactive T-cell responses in mice. Third, the PIV5 AVLP system was used to generate PIV5/HIV chimeric AVLP particles that produce an additional round of infectious particles in vitro and are immunogenic in mice. These studies describe the molecular cloning and generation of the vaccine candidates and their in vitro characteristics as well as their immunogenicity in a mouse model. The work demonstrates that Paramyxovirus-vectored vaccines can induce humoral and cellular responses against HIV.