HIVNONILV

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

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 Obiettivo del progetto (Objective)

'Innovative vectors and strategies are hardly needed to generate safe and efficacious HIV vaccines. Many types of recombinant viruses and DNA vectors have been used to induce protective immunity in the macaque model of HIV vaccine. However, the extent of protection achieved by these vaccines remains disappointing compared to Live-attenuated vaccines. We focused in development of lentiviral-based vectors as DNA vaccines and have shown that our first generation vector was efficient alone to induce protection of monkeys from AIDS following challenge with highly pathogenic homologous virus. We recently characterized the immune responses associated with this protection in immunized macaques. In this project we developed novel lentiviral vectors (lentivector) that have never been tested before. These lentivectors are non-integrating (NONI-LV) into the host genome and are driven by LTRs that have constitutive promoters. These innovative vectors synergize the properties, without the inconvenient, of both DNA and Live-attenuated vaccines. We hypothesize that these vectors will induce responses strong enough to induce protection against heterologous challenge viruses. Our long term goal is to develop safe and efficacious prophylactic vaccines against HIV in humans. The goal of the present project is to evaluate the immunogenicity and the safety of our novel NONI-LV vectors and the protection against pathogenic viruses in the non-human primate model of HIV. The work plan includes 4 major specific aims. In aim 1, we will focus on the safety of this type of vector by demonstrating their inability to integrate into the host genome. In aim 2 we will explore the immunogenicity of this vaccine vector in humanized SCID/NOD mice compared to our first generation vector. In aim 3 we will explore the immune responses induced in monkeys. In aim 4 we will explore the efficacy of induced immune responses to protect immunized monkeys against heterologous pathogenic viruses.'

Introduzione (Teaser)

Novel safe and effective vaccines to induce protective immune responses against HIV in humans are in the pipeline thanks to EU research.

Descrizione progetto (Article)

The 'A novel non-integrating replication limited lentiviral-based vector for HIV vaccination' (HIVNONILV) project has started work on the development of a novel lentivirus vector that is non-integrating (NONI-LV) and replication-limited. This strategy improves the safety of using DNA vaccines as both features carry inherent risks including mutagenesis after insertion in the host genome.

Project members' previous research revealed that these vectors will 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 are evaluating the safety, immunogenicity, and efficacy of their novel NONI-LV vector against pathogenic viruses in the macaque model of HIV vaccine.

Results so far demonstrate that a single dose delivery of the DNA vaccine promoted generation of vaccine-specific CD8+ and CD4+ T cells. Importantly, these have 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.

The work of the HIVNONILV project has important ramifications. Probably the most significant of these is that the DNA vaccine produces particles limited to a single cycle of infection.

HIVNONILV research has been presented at various conferences. Three peer-reviewed papers are being prepared for publication.