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Vectored immunoprophylaxis: an emerging adjunct to traditional vaccination.

ABSTRACT: The successful development of effective vaccines has been elusive for many of the world's most important infectious diseases. Additionally, much of the population, such as the aged or immunocompromised, are unable to mount an effective immunologic response for existing vaccines. Vectored Immunoprophylaxis (VIP) is a novel approach designed to address these challenges. Rather than utilizing an antigen to trigger a response from the host's immune system as is normally done with traditional vaccines, VIP genetically engineers the production of tailored antibodies from non-hematopoietic cells, bypassing the humoral immune system. Direct administration of genes encoding for neutralizing antibodies has proven to be effective in both preventing and treating several infectious diseases in animal models. While, a significant amount of work has focused on HIV, including an ongoing clinical trial, the approach has also been shown to be effective for malaria, dengue, hepatitis C, influenza, and more. In addition to presenting itself as a potentially efficient approach to solving long-standing vaccine challenges, the approach may be the best, if not only, method to vaccinate immunocompromised individuals. Many issues still need to be addressed, including which tissue(s) makes the most suitable platform, which vector(s) are most efficient at transducing the platform tissue used to secrete the antibodies, and what are the long-term effects of such a treatment. Here we provide a brief overview of this approach, and its potential application in treating some of the world's most intractable infectious diseases.

SUBMITTER: Sanders JW

PROVIDER: S-EPMC5531025 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Vectored immunoprophylaxis: an emerging adjunct to traditional vaccination.

Sanders John W JW Ponzio Todd A TA

Tropical diseases, travel medicine and vaccines 20170210

The successful development of effective vaccines has been elusive for many of the world's most important infectious diseases. Additionally, much of the population, such as the aged or immunocompromised, are unable to mount an effective immunologic response for existing vaccines. Vectored Immunoprophylaxis (VIP) is a novel approach designed to address these challenges. Rather than utilizing an antigen to trigger a response from the host's immune system as is normally done with traditional vaccine ...[more]

PMID: 28883973

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Project description:BACKGROUND:A preventive vaccine for HIV is a crucial public health need; adeno-associated virus (AAV)-mediated antibody gene delivery could be an alternative to immunisation to induce sustained expression of neutralising antibodies to prevent HIV. We assessed safety and tolerability of rAAV1-PG9DP, a recombinant AAV1 vector encoding the gene for PG9, a broadly neutralising antibody against HIV. METHODS:This first-in-human, proof-of-concept, double-blind, phase 1, randomised, placebo-controlled, dose-escalation trial was done at one clinical research centre in the UK. Healthy men aged 18-45 years without HIV infection were randomly assigned to receive intramuscular injection with rAAV1-PG9DP or placebo in the deltoid or quadriceps in one of four dose-escalating cohorts (group A, 4 × 1012 vector genomes; group B, 4 × 1013 vector genomes; group C, 8 × 1013 vector genomes; and group D, 1·2 × 1014 vector genomes). Volunteers were followed up for 48 weeks. The primary objective was to assess safety and tolerability. A secondary objective was to assess PG9 expression in serum and related HIV neutralisation activity. All volunteers were included in primary and safety analyses. The trial is complete and is registered with ClinicalTrials.gov, number NCT01937455. FINDINGS:Between Jan 30, 2014, and Feb 28, 2017, 111 volunteers were screened for eligibility. 21 volunteers were eligible and provided consent, and all 21 completed 48 weeks of follow-up. Reactogenicity was generally mild or moderate and resolved without intervention. No probably or definitely related adverse events or serious adverse events were recorded. We detected PG9 by HIV neutralisation in the serum of four volunteers, and by RT-PCR in muscle biopsy samples from four volunteers. We did not detect PG9 by ELISA in serum. PG9 anti-drug antibody was present in ten volunteers in the higher dose groups. Both anti-AAV1 antibodies and AAV1-specific T-cell responses were detected. INTERPRETATION:Future studies should explore higher doses of AAV, alternative AAV serotypes and gene expression cassettes, or other broadly neutralising HIV antibodies. FUNDING:International AIDS Vaccine Initiative, United States Agency for International Development, Bill & Melinda Gates Foundation, US National Institutes of Health.

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Vectored immunoprophylaxis: an emerging adjunct to traditional vaccination.

Publications

Vectored immunoprophylaxis: an emerging adjunct to traditional vaccination.

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