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 vacc
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.
(IMAGE SOURCE/GETTY IMAGES)
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.
Nathalie Garçon, PhD, is the vice president and head of the Global Adjuvant Center for Vaccines at GlaxoSmithKline Biologicals, Wavre, Belgium, +32 (0)1 085 8856, nathalie.garcon@gskbio.com.
Articles by Nathalie Garçon, PhD
Philippe Monteyne, MD, PhD, is the senior vice president of global vaccine development all at GlaxoSmithKline Biologicals
Articles by Philippe Monteyne, MD, PhD,
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