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. 2020 May 30;10(7):1175–1191. doi: 10.1016/j.apsb.2020.05.009

Table 3.

Application of adjuvants in subunit vaccines.

Adjuvant Composition Mechanism Antibody responses and neutralizing antibody Cellular immune response
Alum Aluminum hydroxide/Aluminum phosphate
  • 1

    Promotes a strong Th2-biased response (humoral immune response).

  • 2

    Depot effect

  • 3

    Inflammatory response86
  • 1

    Induces MERS-CoV RBD-specific antibody responses and neutralizing antibodies (1:1600) in rhesus macaque; neutralizes pseudotyped MERS-CoV84.

  • 2

    Induces MERS-CoV RBD-specific antibody responses87.

 No-report
Emulsions
Freund's adjuvant IFA: an water-in-oil emulsion formed by mixing mineral oil with an emulsifier
CFA: killed bacteria M. tuberculosis added to IFA
  • 1

    Continuous release of immunogenic substances in oil droplets.

  • 2

    Inflammatory response.

  • 3

    Stimulates the production of antibodies90, 91, 92

 Induces SARS-CoV RBD-specific antibody responses and neutralizing antibodies (>1:104/1:102–103) in mice; neutralizes pseudotyped and live SARS-CoV93. Elicits SARS-CoV RBD-specific T cell responses in mice93.
Montanide ISA51 IFA
  • 1

    Induces MERS-CoV RBD-specific antibody responses and neutralizing antibodies (>1:103) in mice; neutralizes live MERS-CoV82.

  • 2

    Induces neutralizing antibodies (1:240 ± 139) in mouse; neutralizes live MERS-CoV97.

 No-report
Sigma adjuvant system (SAS) Oil-in-water emulsion containing monophosphoryl lipid A
  • 1

    Enhances antigen uptake at the injection site.

  • 2

    Induces the production of cytokines and chemokines.

  • 3

    Recruits immune cells to the injection site98, 99, 100.
  • 1

    Induces SARS-CoV RBD-specific antibody responses and neutralizing antibodies (1 : 6.9×105/1 : 1.6×103) in mice; neutralizes pseudotyped and live SARS-CoV101.

  • 2

    Induces neutralizing antibodies (1:102‒103) in mice; neutralizes eight MERS-CoV strain102.

 No-report
MF59 Squalene-based oil-in-water emulsion
  • 1

    Induces MERS-CoV RBD-specific IgG subtype antibody (IgG1 and IgG2a) and neutralizing antibodies (1:100–673) in mice; neutralizes live MERS-CoV103.

  • 2

    Induces MERS-CoV S1-specific IgG subtype antibody (IgG1 and IgG2a) and neutralizing antibodies (1:103‒104) in mice; neutralizes pseudotyped and live MERS-CoV104.

 No significant increase in T-cell response28.
Toll-like receptors (TLRs) agonists
TLR3 agonist Double-stranded RNA (dsRNA) analogue
  • 1

    The recognition of receptor stimulates innate immune responses such as antiviral and inflammatory responses.

  • 2

    Induce adaptive immune responses.

  • 3

    Activate immune cells and induce the production of Cytokines106,107.

 No-report
  • 1

    Induces the expression of IFN-associated molecule, elicits T cell responses110.

  • 2

    Induces the production of type-I IFN, elicits T cell responses111.
TLR4 agonist LPS/MPLA Induces SARS-CoV S-specific antibody and virus-specific antibody (>1:104)116. Induces the production of Th1 cytokines, elicits T cell responses116.
TLR9 agonist CpG DNA No-report
  • 1

    Induces the production of IFN-a and IFN-γ, enhance NK cell cytotoxicity120.

  • 2

    Induces cytotoxicity T cells response and memory T cells response121.
Stimulator of interferon genes (STING) agonists
STING agonist cdGMP
  • 1

    Activates the production of host defense molecules and cytokines.

  • 2

    Induces adaptive immune responses123,124.

 Induces MERS-CoV RBD-specific IgG subtype antibody (IgG1 and IgG2a) and neutralizing antibodies (1:40–320) in mice; neutralizes live MERS-CoV126. Induces the production of IFN-γ and memory T cells response126.