A roadblock in the development of effective treatments and vaccines for HIV is the large degree of genetic variation present between strains. Previous vaccines based on HIVconsv proteins have suffered from suboptimal coverage owing to these genetic differences.
Oxford researchers have expanded on the HIVconsv methodology, developing a series of chimaeric immunogenic proteins, tHIVconsvX (X = 1-6), which offer far greater coverage. Consisting of several highly conserved regions of the HIV proteome the polypeptides are combined in a manner that reduces irrelevant, anti-junctional immune responses, thus increasing the efficiency and coverage of the cytotoxic T-cell (CTL) response.
Human Immunodeficiency Virus (HIV)
In 2015 it was estimated that 37.7 million people were living with HIV with the number of new infections estimated at 2.1 million. The disease resulted in
1.1 million deaths from AIDS-related illnesses. The development of new treatments for the disease is hampered by the genetic diversity of the virus.
Delivered by simian adenovirus ChAdV63 and poxvirus MVA, the 1st-generation conserved vaccines were tested in 8 trials in UK, EU and Africa and showed high immunogenicity, replication control in vitro of 4 major HIV clades A, B, C and D and, in a pilot study in combination with early ART (Antiretroviral therapy) and latency-reverting agent Romidepsin, produced a signal of viremic control during monitored ART pause in 36% of vaccine recipients. The vaccines with Vorinostat were also used in the first randomized blind ‘kick and kill’ trial RIVER.
Learning from the trials, the researchers from Oxford and Los Alamos National Laboratory had an opportunity to upgrade the immunogens. The main improvements of the 2nd-generation tHIVconsvX include a bioinformatics-assisted redefinition of conserved regions, inclusion of protective & conserved epitopes and maximizing vaccine match to global HIV variants by bivalent mosaic design, while induction of responses against inter-regional junctions was minimized by a region scramble.
Administering the tHIVconsvX proteins as pairs using different vaccine modalities ensures a maximum match to global circulating HIV and the induction of effective, robust immunity.
The main benefits of this vaccine:
- Computer-optimised mosaic sequences designed to yield maximum HIV epitope match
- Effective and robust cytolytic T cells against the most vulnerable parts of the virus
- Could be used as part of a therapeutic or prophylactic vaccine
Oxford University Innovation has filed a priority patent covering this project (WO2015048785A3 – Mosaic conserved region HIV immunogenic polypeptides) and is seeking partners to help commercialise the technology.
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