Immune responses to viral proteins with a high rate of variation are not protective over the longterm. Variation can come from antigenic drift or shift. Antigenic drift is the accumulation of small changes to viral genes encoding proteins targeted by the immune system that happen regularly, as the virus replicates. Antigenic shifts are more abrupt changes to viral genes leading to either new subtypes, or jumps from species to species (i.e. animals to humans). Immune targeting of viral proteins susceptible to antigenic drift or shift allows viruses to evade the immune response.
We design vaccines to generate an immune response to the conserved regions of viral proteins. These regions have not evolved over time and remain broadly the same across different strains. Conserved regions typically reside in internal proteins and those serving important functional roles. Their internal location tends to protect them from immunological pressure, and their functional importance also makes them less likely to be subject to changes that could lead to loss of function which could impact virus viability and infectivity.
By anticipating antigenic drift and antigenic shift in this way, we develop vaccines which can provide lasting protection against emergent pandemic virus strains.
What We Do
We use a novel in silico proprietary platform to identify highly conserved regions of viral proteins that contain a high number of reactive T-cell epitopes with extensive HLA coverage.
These regions are then used as antigens and are delivered using the most appropriate method for the combination of antigens and the disease, for example, as synthetically-manufactured peptides or encoded in an mRNA construct encased in lipid nanoparticles or nanolipoprotein particles.
Our approach has consistently identified promising vaccine candidates which have demonstrated immunogenic responses in pre-clinical validation studies and have achieved mid- and late-stage clinical milestones.
The pipeline is secured by 167 granted patents with 22 patent applications pending and three applications being prepared.
Synthetic multi-epitope peptides identified in silico induce protective immunity against multiple influenza serotypes. Stoloff GA, Caparros-Wanderley W.
Eur J Immunol. 2007 Sep;37(9):2441-9. doi: 10.1002/eji.200737254. PMID: 17668898View publication
Synthetic Influenza vaccine (FLU-v) stimulates cell mediated immunity in a double-blind, randomised, placebo-controlled Phase I trial.
Pleguezuelos O, Robinson S, Stoloff GA, Caparrós-Wanderley W. Vaccine. 2012 Jun 29;30(31):4655-60. doi: 10.1016/j.vaccine.2012.04.089. Epub 2012 May 8. PMID: 22575166View publication
A Synthetic Influenza Virus Vaccine Induces a Cellular Immune Response That Correlates with Reduction in Symptomatology and Virus Shedding in a Randomized Phase Ib Live-Virus Challenge in Humans.
Pleguezuelos O, Robinson S, Fernández A, Stoloff GA, Mann A, Gilbert A, Balaratnam G, Wilkinson T, Lambkin-Williams R, Oxford J, Caparrós-Wanderley W. Clin Vaccine Immunol. 2015 Jul;22(7):828-35. doi: 10.1128/CVI.00098-15. Epub 2015 May 20. PMID: 25994549View publication
Meta-Analysis and Potential Role of Preexisting Heterosubtypic Cellular Immunity Based on Variations in Disease Severity Outcomes for Influenza Live Viral Challenges in Humans.
Pleguezuelos O, Robinson S, Fernandez A, Stoloff GA, Caparrós-Wanderley W. Clin Vaccine Immunol. 2015 Aug;22(8):949-56. doi: 10.1128/CVI.00101-15. Epub 2015 Jun 17. PMID: 26084515View publication
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