Addressing Unmet Medical Needs Through Tailored Vaccine Design: The Importance of Adjuvant Systems

It is now possible to combine antigens with specific adjuvant systems to create more-effective vaccines.
Oct 01, 2009


The development of new vaccines has progressed from an empirical approach to more sophisticated vaccine design. This has been enabled by advances in our understanding of the immune system and by improvements in immunological tools, particularly the use of new adjuvant combinations. It is now possible to combine an antigen with a specific adjuvant system to design effective vaccines that provide an immune response tailored for each vaccine. The clinical application of the antigen–adjuvant system concept has shown benefits for diseases like pandemic influenza and human papillomavirus (HPV) cervical cancer. Observed benefits include higher and sustained immune response (humoral and cell mediated) and immune memory, cross-type immunity, and antigen-sparing, along with a favorable safety profile. The advantages of using an adjuvant system in the preventive field also have generated interest in the context of therapeutic vaccines, particularly in cancer immunotherapy. Strong signals of clinical activity of MAGE-A3 antigen-specific cancer immunotherapeutics (ASCI), demonstrated in proof-of-concept studies in melanoma and non-small cell lung cancer (NSCLC), have prompted the start of two large pivotal Phase 3 trials. The tailored antigen–adjuvant system combination approach is thus opening new possibilities for designing effective vaccines against unmet medical needs.

The future of vaccine development is based on the ability to address remaining unmet medical needs linked to challenging pathogens or challenging populations. There are no vaccines available yet to fight leading infectious killers including challenging pathogens such as parasites requiring complex, multistage immune responses (malaria), highly variable viruses that evade or subvert the immune response (hepatitis C, AIDS), or mycobacteria (tuberculosis). In addition, novel vaccine strategies are needed to target new pathogens with pandemic potential such as new influenza strains, because during a pandemic, large populations will have to be immunized in short time. Other challenges include the improvement of currently established vaccine strategies to address the aging of the immune system (immunosenescence) in the elderly population or a better protection of individuals with impaired immune response caused by chronic conditions or immunodeficiency. Finally, new approaches are needed when using antigens that have weak immunogenicity (highly purified proteins and peptides, polysaccharides etc.) or are prone to genetic drifting (seasonal influenza).

A unique feature of the human immune system is its ability to recall an encounter with a disease-causing pathogen for decades, even over the course of a lifetime. This fundamental property of the immune system is the basis for vaccination. The goal of any successful vaccine is to induce a strong priming of the immune system. This should translate to a high and sustained immune response, as well as strong stimulation of the immune memory that should provide long-term protection against a specific disease. Vaccine design begins with the identification of the immune pathway responsible for protecting against a particular disease. The antigen, i.e., the targeting component of the vaccine, is then selected for its ability to elicit a desired immune response. The second step is the selection of adjuvant(s), because vaccines with inactivated pathogens or purified subunit antigens are usually less immunogenic compared to vaccines with live-attenuated pathogens. Therefore, the addition of compound(s) able to enhance the immune response towards the administered antigen is required. The added value of adjuvants in vaccine development was discovered more than 80 years ago when aluminium salts were first used in vaccine formulation.1

The better understanding of the immune system, especially the interaction between the innate and adaptive immune response, and the use of adjuvants, have enabled the formulation of vaccines better tailored to the needed immune response.2–3

Adjuvant systems are designed to enhance protection in cases where the classical single adjuvant approach has proven to be insufficient or incapable of providing optimal protection, i.e., for specific populations or challenging diseases. The aim in designing a vaccine adjuvanted with an adjuvant system is to optimize the vaccine's interaction with the immune system's response to the vaccine through synergy between the antigen and the selected adjuvant system.

The target population, the antigen, the route of administration, the type of desired immune priming, and the required duration of immunity all influence the choice of the most appropriate adjuvant system for a given vaccine.