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A NOVEL NON-INTEGRATING REPLICATION LIMITED LENTIVIRAL-BASED VECTOR FOR HIV VACCINATION

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A renewed attack on HIV

Development of a prophylactic vaccine that stops HIV infection remains a high priority. A novel safe and effective approach to induce immune response against HIV is in the pipeline thanks to EU research.

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The HIVNONILV (A novel non-integrating replication limited lentiviral-based vector for HIV vaccination) project worked on the development of a novel lentivirus vector that is non-integrating (NONI-LV) and replication-limited. This would improve the safety of DNA vaccines as current classical vectors carry inherent risks including mutagenesis after insertion in the host genome. Project members' previous research revealed that these vectors induce protective immune responses against challenge viruses. These challenge viruses, based on the monkey equivalent of HIV, simian immunodeficiency virus (SIV), are notoriously hard to control by vaccination. HIVNONILV researchers evaluated the safety, immunogenicity, and efficacy of their novel NONI-LV vector against pathogenic viruses in the macaque model of HIV vaccine. Results clearly demonstrated that a single dose immunisation with only DNA (producing single cycle viral particles) promoted generation of vaccine-specific CD8+ and CD4+ T cells. It caused immediate and recallable immune activity even in the absence of persistent antigen stimulation. So far, this has only been achieved using replication-competent and persistent recombinant HIV viral vectors. After development of productive infection, a 100 % of the vaccinated macaques had greater than one log reduction in the peak of viraemia compared to control animals. They maintained lower viraemia during the early and the late chronic phase of infection. Such impressive viral control is linked to the reactivation of memory T cell responses in the vaccinated group. Historically, vaccines represent the most effective way to control global infectious diseases. HIVNONILV studied novel vector and vaccination strategies making an important contribution to the HIV-1 vaccine field.

Keywords

HIV, vaccine, immune response, HIVNONILV, lentivirus vector, replication-limited

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