Classification of Immune Adjuvants and Progress in the Study of
Their Mechanisms of Action
Yuting Fu
Department of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou, China
Keywords: Immune Adjuvants, Vaccine Development, Mechanism of Action.
Abstract: Immunological adjuvants are indispensable in vaccine development and immunotherapy, serving as pivotal
elements that amplify the immune system's response to antigens. These substances are extensively employed
to bolster the immunogenicity and longevity of diverse vaccines. In immunotherapy, adjuvants treat numerous
diseases, modulating and enhancing the body's defense mechanisms. This paper collates recent research on
immune adjuvants' categorization and modes of action, meticulously examining the distinct attributes of
various adjuvant types. It encapsulates their mechanisms of action and the potential for their utilization in
vaccine formulation and immunotherapeutic strategies. It provides a robust theoretical foundation for crafting
future vaccines and enhancing immunotherapeutic approaches. In conclusion, exploring immunological
adjuvants is critical in advancing vaccine science and immunotherapy. By understanding the mechanisms and
classifications of these substances, researchers can optimize vaccine efficacy and tailor immunotherapeutic
interventions to combat a range of diseases more effectively. The insights gained from this research enhance
our theoretical grasp and pave the way for practical applications that could significantly improve public health
outcomes. As we continue to unravel the complexities of the immune system, the role of adjuvants will
undoubtedly remain central to developing innovative solutions in the fight against infectious diseases and
beyond.
1 INTRODUCTION
The immune system's efficiency, as the core barrier
of the body's defense against pathogens, directly
impacts the protective effect of vaccines. Many
antigens (e.g., recombinant proteins, synthetic
peptides, etc.) have difficulty triggering a sufficiently
strong immune response due to their simple
molecular structure or weak immunogenicity
(Janeway et al.1992). The emergence of immune
adjuvants has provided a key breakthrough to solve
this problem. By synergizing with antigens, adjuvants
can significantly enhance specific antibodies and
cellular immune responses, making the development
of immune adjuvants one of the core technologies in
modern vaccine development (Gupta et al.1995).
According to the World Health Organisation (WHO),
about 30% of the world's vaccines rely on adjuvants
to enhance the immune effect, especially in new types
of vaccines, such as cancer and genetically
engineered vaccines. The role of adjuvants is even
more critical.
Historically, the study of immune adjuvants can
be traced back to the early 1900s. 1926 saw the first
discovery by Ramon that alum enhanced antibody
production to diphtheria toxin, initiating the study of
adjuvants, and the introduction of Freund's adjuvant
in the 1950s led to the rapid development of
experimental immunology (Pardi et al. 2018). Still, its
clinical use was severely limited by its limitation of a
vigorous inflammatory response. This was strictly
limited due to the restriction of a strong inflammatory
response and the clinical application of Freund's
adjuvants. In the last decade, with the breakthroughs
in immunological theories and advances in
nanotechnology, significant progress has been made
in the research and development of novel adjuvants,
such as lipid nanoparticles (LNP) and CpG
oligonucleotides, which provide new ideas to address
the safety and efficacy of traditional adjuvants
(Oleszycka et al. 2018).
However, current adjuvant research still faces
multiple challenges. Some adjuvants (e.g., aluminum
salts) only induce Th2 type immune response and
have limited effect on pathogens that require Th1 type
Fu, Y.
Classification of Immune Adjuvants and Progress in the Study of Their Mechanisms of Action.
DOI: 10.5220/0014464400004933
Paper published under CC license (CC BY-NC-ND 4.0)
In Proceedings of the 1st International Conference on Biomedical Engineering and Food Science (BEFS 2025), pages 203-206
ISBN: 978-989-758-789-4
Proceedings Copyright © 2026 by SCITEPRESS – Science and Technology Publications, Lda.
203

response (e.g., viruses, intracellular bacteria) (Kool et
al. 2008). In addition, the mechanism of action of
adjuvants has not been fully elucidated, and in
particular, the mechanism of interaction between
nano-adjuvants and the immune system remains
controversial. The lack of systematic theoretical
guidance for personalised adjuvant design limits the
development of disease-specific vaccines (McKernan
et al. 2020). Therefore, an in-depth analysis of the
classification and mechanism of action of adjuvants
is of great scientific significance and clinical value for
optimizing the performance of existing vaccines and
developing new vaccines (Takeuchi et al.2010).
2 CLASSIFICATION OF
ADJUVANTS
According to the composition of immune adjuvants,
adjuvants can be classified into chemical inorganic
adjuvants, chemical organic adjuvants, synthetic
adjuvants, and biological cytokine adjuvants. Their
composition, characteristics, mechanism of action,
scope of application, and disadvantages are shown in
Table 1.
Table 1. Their composition, characteristics, action mechanism, application scope, and disadvantages.
Adjuvant
Category
Ingredient Specificities
Mechanism of
action
Scope of
application
Drawbacks
Chemical
inorganic
adjuvant
Aluminium salt
adjuvants e.g.
Al(OH)₃, AlPO₄,
calcium salts (Lin et
al. 2018)
Highly safe and easy to
prepare
Calcium salt adjuvants
are less commonly
used and gradually
replace aluminium
salts due to their high
biocompatibility (Jinsu
et al.2024).
Formation of
antigen-adjuvant
complexes and
enhancement of the
immune response.
Hepatitis B
vaccine, HPV
vaccine, etc.
Th2 bias and localized side
effects limit applications
Chemical,
organic
adjuvant
Oil emulsion,
liposome adjuvant
(c, polysaccharide
adjuvant
(Ganoderma
lucidum, Angelica
sinensis), soap base
(QS-21), etc.
(Jiangsu et al.
2024).
Chemical and organic
adjuvants are
commonly added to
vaccines to reduce
antigen use and
improve vaccine
immune persistence.
May optimise the
balance and
efficiency of the
immune response
by regulating
interactions
between immune
cells (Li jet al.
2024; Li 2023).
Immunological
effects at mucosal
sites include the
intestine and oral
cavity with
machines, zosters,
coronavirus, etc.
Although well-expressed
short-term trials are safe,
issues such as long-term
toxicity that arise need to be
evaluated in more long-
term follow-up studies (Li
jet al. 2024; Li 2023).
Synthetic
adjuvant
CPG
oligonucleotide
POLY L
:C, etc.
Sequences can be
designed to optimize
their immune
activation effect and
target specific diseases
according to different
needs (Kayraklioglu et
al. 2021).
For example, the
ability of CpG
ODN to stimulate
innate and adaptive
immune responses
in humans and
various animal
species
Hepatitis B
vaccine, influenza
vaccine, HPV
vaccine, HIV
vaccine, etc.
In some cases, non-specific
activation of other immune
cells or signaling pathways
may lead to a lack of
precision in
immunomodulation and
potentially increase the risk
of side effects (Chen et al.
2021)
Cytokine
adjuvant
Interleukins: e.g.
IL-2, IL-4, IL-12,
GM-CSF, IFN-γ,
etc.
One cytokine can act
on multiple target cells
and produce various
regulatory effects;
different cytokines can
also act on the same
target cells and
produce the same or
similar biological
activities (Firdaus et al.
2022).
Inducing multiple
cytokines to form a
complex cytokine
network that finely
regulates immune
cells' proliferation,
differentiation and
functioning
(Michalak et al.
2022).
HIV, influenza,
rabies, hepatitis B
virus (HBV),
hepatitis C virus
(HCV), etc.
Cytokine interactions are
complex and require
precise design and optimal
combinations when applied
in combination. Otherwise,
the desired immune-
enhancing effects may not
be achieved, or even
antagonism or increased
risk of side effects may
occur.
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3 MECHANISMS OF ACTION OF
IMMUNE ADJUVANTS
Different immune adjuvants play other roles, and
cells broadly, their mechanisms of action can be
divided into three categories.
Antigen Delivery Enhancement Adjuvants
enhance antigen delivery by forming antigen
reservoirs and slowly releasing antigenic liposomes
and nanoparticles (Ding et al.2023).
Immune cell activation Adjuvants enhance
immune cell response by activating pattern
recognition receptors such as TLR. Cytokine
adjuvants can regulate the function of immune cells,
such as promoting the proliferation and
differentiation of T cells and enhancing the
phagocytosis of macrophages. By controlling the
cytokine network, cytokine adjuvants can synergize
with other immune adjuvants to enhance the immune
effect of the vaccine. In addition, cytokine adjuvants
can also regulate the migration and localization of
immune cells so that they can reach the site of an
infection more effectively and play an immune role
(Tao et al., 2023).
Immune Response Modulation Adjuvants
enhance the immune response by regulating the
Th1/Th2 balance. Novel adjuvants enhance antiviral
immune response by activating the STING pathway
(Duan et al. 2025).
4 PROSPECTS FOR THE
APPLICATION OF IMMUNE
ADJUVANTS
4.1 Vaccine Development—The Use of
Adjuvants in Novel Vaccines
Adjuvants, as an essential component of vaccines, can
significantly enhance the immune response to a
vaccine, thereby improving the protective efficacy of
the vaccine. The use of adjuvants is becoming
increasingly common in developing novel vaccines,
especially in vaccines that are difficult to elicit an
adequate immune response, and the role of adjuvants
is particularly critical. Complex adjuvants further
optimize the immune effect of vaccines by combining
multiple immune-enhancing mechanisms and offer
new possibilities for vaccine development (Ben-
Akiva et al. 2025).
For instance, the adjuvant MF59, used in the
influenza vaccine, has been shown to boost the
immune response in the elderly, a population group
that often has a weaker response to vaccines (Ko et al.
2018). Similarly, AS03, another oil-in-water
emulsion adjuvant, has been utilized in the H1N1
influenza vaccine to enhance the immune response
and provide broader protection against various strains
(Cohet et al. 2019). In addition, the adjuvant system
AS01 has been successfully applied in the shingles
vaccine, demonstrating its ability to elicit a strong and
durable immune response. As research continues
(Didierlaurent et al. 2017), developing new adjuvants
with improved safety profiles and enhanced efficacy
will be crucial for the future of vaccine innovation,
particularly in the fight against emerging infectious
diseases.
4.2 Immunotherapy—The Use of
Adjuvants in Tumor
Immunotherapy
Adjuvants play an essential role in vaccine
development and show excellent application
prospects in immunotherapy. In tumor
immunotherapy, adjuvants can activate and enhance
the body's immune response to tumor cells, thus
contributing to tumor clearance. Meanwhile, the
potential of adjuvants in treating autoimmune
diseases should not be overlooked. By modulating the
immune system's response, adjuvants have the
potential to become a new strategy for treating
autoimmune diseases. These applications
demonstrate the diverse potential and future direction
of adjuvants in immunotherapy. In conclusion,
adjuvants are pivotal in enhancing the efficacy of
immunotherapies, whether in combating cancer or
managing autoimmune conditions. Their ability to
fine-tune the immune response highlights their
significance in advancing personalized medicine. As
research progresses, optimizing adjuvant use could
lead to breakthroughs in treating various diseases,
offering hope for improved patient outcomes (Dredge
et al. 2002; Jeon 2023).
5 CONCLUSION
Immunological adjuvants are key components in
enhancing the effectiveness and durability of vaccine
immunity. Adjuvants are classified as chemically
inorganic, chemically organic, synthetic and cytokine
adjuvants, each with their characteristics and scope of
Classification of Immune Adjuvants and Progress in the Study of Their Mechanisms of Action
205

application. Still, challenges, such as safety and
mechanisms of action, are not entirely clear.
They play an essential role in vaccine
development and immunotherapy. They enhance
antigen presentation, activate immune cells and
modulate the immune response in their respective
roles in three pathways. They can improve the
effectiveness of vaccines by activating specific
immune cells and modulating the type and strength of
the immune response. As molecular biology and
immunology continue to advance, the study of
immune adjuvants is also seeing new development
opportunities. Scientists are now trying to design
more precise and efficient adjuvants using cutting-
edge technologies such as nanotechnology and gene
editing. For example, the synthetic adjuvant CPG
oligonucleotide can be sequence-designed to
optimize its immune-activating effect and target
specific diseases according to different needs. In
addition, the concept of vaccines is emerging,
whereby an individual's immune genotype is
analyzed to other populations, personalized tailor
adjuvants and vaccines that are best suited. These
innovations will advance the development of
vaccinology and the treatment of various infectious
and specific diseases, bringing new hope for chronic
diseases. Through these studies, scientists can
provide new ideas and methods for vaccine design
and immunotherapy, which will lead to the
development of safer, more effective and more
targeted vaccines and treatments and ultimately make
more significant contributions to human health.
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