Chemicals & raw materials
immune response, from how the adjuvants activate our immune system in the first place to how it responds to a vaccine eventually. We’re trying to understand all of those steps.”
How close are we to realising the potential of adjuvants? While research is wide-ranging and ongoing, we can look to some promising areas of investigation for a sense of where the field is headed.
The guarantees “We know that, generally speaking, adjuvants induce inflammation, they induce irritation of our biological systems, and those inflammatory processes then enhance the immune response to the vaccine that is given with the adjuvant,” says Dr Milicic. These processes work to mimic the body’s natural immune response, effectively tricking it into responding as if it had come into contact with a virus or bacteria. Over the past few decades, we’ve learned more about how adjuvants can be used, including the 2011 Nobel-prize winning discovery that innate immunity (our body’s natural defence system) drives adaptive immunity (immunity that we acquire after being exposed to a disease). Toll-like receptors (TLRs), a class of proteins, were recognised as playing a crucial signalling role in this process, and several adjuvants that initiate a TLR response have since been approved for use in licenced products. More adjuvants have been discovered in recent decades than in the past 80 years, with research spurred on by increased funding and institutional support in light of the pandemic. The NIH, for example, established adjuvant discovery and development programmes within its already- established consortiums, leveraging assets among public and private organisations to rapidly respond to the current, as well as future, pandemics. The research process carried out on potential adjuvants must consider what type of immune response needs to be induced to protect against a certain disease, and then determine which substance or substances in combination can create that response, says Dr Milicic. “We need to join the dots between all those things to get a bigger, better picture.” Adjuvants that are currently approved for use include aluminium salts (Alum), certain oil-in-water emulsions, and types of saponins, a plant-derived compound.
The right combination
For each virus or bacteria, there could be multiple adjuvants that trigger the immune response when combined with an antigen, says Krishnendu Roy, professor and Robert A. Milton chair in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. And now, there’s increasing interest in how these can be combined in certain ways to create the desired or even a greater effect.
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“We have tried single-agent vaccines for many years, in many things. But in diseases where either the virus or bacteria has figured out how to avoid the immune system, or the vaccine response hasn’t been strong, I think it’s absolutely rational to try combination adjuvants,” says Roy.
When adjuvants are combined, there are certain attributes that Dr Ofer Levy, Harvard Medical School professor, physician, and director of the Precision Vaccines Programme, and his team look for when evaluating the potential of the substance. “You could get additivity, antagonism, or synergy. We look for synergistic combinations and those interactions that are age-specific,” he says.
Synergistic combinations are when combined molecules produce a unique effect beyond being a simple summation of their individual effects (additive), and that is greater than if they were given alone.
We have tried single-agent vaccines for many years, in many things. But in diseases where either the virus or bacteria has figured out how to avoid the immune system, or the vaccine response hasn’t been strong, I think it’s absolutely rational to try combination adjuvants.”
Krishnendu Roy, Georgia Tech and Emory University
Once a substance is identified, it’s evaluated based on its efficacy and toxicity – the adjuvant needs to work well while also being safe to use, says Roy. However, the jury is still out on whether combination adjuvants are more effective across the board than single adjuvants, he adds. So far, though, combination adjuvants have shown promise. The first combination adjuvant to be licenced was AS04 in 2005, developed by GlaxoSmithKline (GSK). It combines a TLR agonist with Alum and today is used in a HPV vaccine (Cervarix), which is
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Adjuvants that are currently approved for use include aluminium salts (Alum), certain oil-in-water emulsions, and types of saponins, a plant-derived compound.
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