Issue 4: Adjuvants: Adding Impact to Speed

Apr 22, 2020

By Ted Schenkelberg, M.B.A., M.P.H.

Chief Operating Officer

In response to SARS-CoV-2, several companies are making available adjuvants that have been used in licensed vaccines. (Credit: NIAID-RML)

While vaccines are hoped to play the starring role in ending the pandemic, it may just be a supporting cast of adjuvants that allow these vaccines to reach their full potential. Adjuvants can be particularly impactful in a pandemic, and in the case of COVID-19 they may be essential, given that a significant portion of the global vaccine portfolio is made up of subunit vaccines that lack the immunogenicity of both natural infection and live attenuated vaccines.

Adjuvants are additives to vaccines that enhance and modulate immune responses by stimulating innate immunity, the immune system’s network of first responders. Many adjuvants take advantage of the innate immunity’s ability to recognize molecular signatures which are common across many invading pathogens via pattern recognition receptors (PRRs). Activating innate immunity, adjuvants set off a cascade of immunological events, which influence the type, quality, and magnitude of the adaptive immune response. 

The most widely used adjuvant is alum mostly in the form or aluminum salts, which has been safely used in billions of doses since the 1920s to generate enhanced antibody responses. Despite this track record, advanced adjuvant development is still in its relatively early stages. Only a handful of adjuvants have actually been used in licensed vaccines, and the mechanisms of action for even the earliest alum-based adjuvants are just now being understood. Further adjuvants must be considered in the context of each vaccine for development and licensure, and can pose unique safety and risk-benefit issues as in the case of the 2009 H1N1 pandemic vaccine. That said, the field of adjuvants is expanding with new classes used to modulate specific types of adaptive responses such as T-cell immunity, particularly important for subunit vaccines.

In relation to adjuvants, vaccines can broadly be broken down into two categories: live attenuated vaccines which essentially contain their own adjuvants, and whole-killed, subunit or DNA/RNA vaccines which do not. Traditionally live attenuated vaccines, have been the gold standard including measles, polio, smallpox and yellow fever. Based on whole versions of a pathogen – including the common molecular signatures recognized by PRRs – these vaccines essentially include their own adjuvants, and induce immune responses nearly identical to natural infection that is often highly effective and long lasting across populations.

In contrast, subunit vaccines including DNA/RNA vaccines are based on only a targeted portion of viral proteins or genetic material. Such vaccines offer speed of development, but often have more limitedimmunogenicity, require multiple doses and elicit shorter term immunity. In the context of pandemic, adjuvants can help overcome the limitations of subunit vaccines in several ways:

  1. Dose Sparing: When billions of doses are needed rapidly, every dose counts. Adjuvants can play an important role in stretching limited manufacturing capacity by reducing the required antigen in each dose. Dose sparing has been considered for pandemic influenza and polio eradication where adjuvants might allow just 10 percent of the standard amount of antigen to be used in each dose.  
  2. More Rapid Protection:  A single shot vaccine can extend population-based protection more rapidly, reduce costs and spare limited manufacturing capacity. Adjuvants such GSK’s AS04 formulation have been shown to reduce the number of doses required for immunological protection, allowing developers to come closer to the one shot ideal. 
  3. Protecting Vulnerable Populations: Last week we looked at the need of protecting vulnerable populations of older adults. Adjuvants have been shown to improve vaccine responses in the highest risk groups for COVID-19 including adults over 65immunocompromised individuals and those with chronic disease

In response to COVID-19, several companies are making available adjuvants that have been used in licensed vaccines including: 1) GSK (ASO3 adjuvant in collaboration with SanofiUniversity of QueenslandClover Biopharmaceuticals and Xiamen Innovax Biotech), 2) Dynavax (CpG 1018 adjuvant in collaboration with University of QueenslandSinovac and Clover Biopharmaceuticals) and 3) CSL/Seqirus (MF59 adjuvant in an early stage collaboration with the University of Queensland). Numerous other groups such as the Precision Vaccines Program are looking to include novel adjuvants in COVID-19 vaccines. 

Many initial vaccines being developed have traded speed for immunogenicity in their response to the pandemic. Adjuvants may be able to play an important role in helping to overcome platform limitations, and ensure more effective and widely used COVID-19 vaccines.

Register for the HVP COVID Report: