T-cell priming vaccines offer the potential to provide faster, broader and longer lasting immunity to reduce serious illness associated with infectious diseases such as COVID-19. Here’s why…
The human immune system has evolved over millennia and includes a multitude of different immune effector cells, antibodies and signalling molecules. As our knowledge of this complex system grows, new scientific insights may provide clues on how to develop new and more effective vaccines.
This is particularly relevant and timely as SARS-CoV-2 variants emerge and spread globally, causing further outbreaks of COVID-19 around the world.
The need for innovation to develop new vaccines
At a basic level, the aim of a vaccine is to prepare the body to have the capacity to turn a dangerous pathogen into a mild irritant and reduce the chance of onward transmission. RNA viruses, like SARS-CoV-2, exist as viral quasispecies or mutant clouds – populations of large numbers of variant genomes subject to constant change due to replication errors, so viral mutation and new dominant variants are inevitable.
Antibody generating vaccines have helped reduce the severity of COVID-19 disease but may offer more limited protection from new viral variants1, for which viral variant booster vaccines may be required in the future. There is an acute need for innovation to explore new vaccines that provide broader, mutation agnostic and longer-lasting immunity. In addition, we need vaccines that are easy to store and administer, reducing the demands on our healthcare systems.
Antibody generating vaccines
Antibodies are large Y shaped protein molecules produced by the B lymphocyte cells of the immune system and which circulate in the blood and bind to ‘foreign objects’, including pathogens such as viruses. Antibody-generating vaccines are well established and operate through the production of viral-specific antibodies. These attach to specific parts of the viral structure (such as Spike protein in SARS-CoV-2) allowing extracellular virions to be cleared from the body by other cells in the immune system.
However, viruses mutate at many points especially surface proteins; if this includes the antibody target it may reduce the efficacy of the vaccine. It is important to note that viruses replicate using the host cells apparatus and once inside a cell, are ‘hidden’ from circulating antibodies.
The case for T-cell priming vaccines
T-cells are a type of white blood cell, and one of the most important roles they serve in the immune system is identifying and killing viral infected cells from the body, preventing viral replication. Infected cells express ‘marker’ peptides on their surface, some of which will come from the infecting virus and many of which will be highly conserved (unlikely to be subject to mutation) and unique to families of viruses. ‘Priming’ naïve T-cells (naturally occurring CD8+ T Lymphocytes) prepares the body to recognize these markers of cellular infection and the body creates virus specific T-cells in readiness for subsequent exposure to that pathogen. Once ‘primed’, a subsequent exposure to the virus is rapidly met by an ‘army’ of virus specific cytotoxic T-cells, which can kill infected cells before they can produce active viruses through replication – thus an infection is never allowed to take hold.
A T-cell response targets the infected cells (the ‘virus factories’) and not the virus itself using a large number of ‘marker’ peptides derived from many parts of the viral structure– so mutations of the virus are less likely to lead to a loss of efficacy as the cellular markers of infection are often highly conserved peptides from the virus.
T-cell priming vaccines still allow the body to undergo its natural immune response to a subsequent infection (for example, the creation of neutralizing antibodies), however this will not be driven by high levels of live, replicating viruses as the T-cell response will be immediate and viral replication is likely to be halted before an active infection can take hold. T-cell based immunity has been shown to last for decades and so T-cell priming vaccines offer the hope for a much broader and longer lasting immune response2.
Emergex is developing next-generation T-cell priming vaccines to tackle major global diseases. T-cell priming vaccines offer potential efficacy against a range of viral pathogens including Coronavirus, Dengue, Influenza, Zika, Yellow fever, as well as intracellular bacteria. Find out more about our approach at www.emergexvaccines.com.