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TLR4-dependent adjuvant activity of Neisseria meningitidis lipid A
Susu Zughaier1, Liana Steeghs, Peter van der Ley
1Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 1440 Clifton Road NE, Atlanta, GA 30322, USA.
Abstract:
The adjuvant activity of Neisseria meningitidis serogroup B lipopoly(oligo)saccharide (LOS) from wild-type and genetically defined LOS mutants and unglycosylated meningococcal lipid A was assessed in C3H/HeN and C3H/HeJ mice. Meningococcal lipid A, a weak agonist for TLR4/MD-2 in human macrophages, was found to have adjuvant activity similar to that of wild-type and KDO(2)-lipid A LOS in C3H/HeN mice. All meningococcal LOS structures as adjuvants induced high titers of IgG1, IgG2a and IgG2b but very little IgG3 to OMP compared to no adjuvant PBS controls. In addition, induced OMP antibodies were shown to have high bactericidal activity against serogroup B meningococci. Purified LOS and lipid A structures failed to induce any adjuvant activity in C3H/HeJ mice indicating that meningococcal LOS as an adjuvant was TLR4-dependent. Unglycosylated meningococcal lipid A because of its weak agonist activity for human macrophages and retention of adjuvant activity may be a candidate for use in serogroup B meningococcal OMP and OMV vaccines and for use as an adjuvant in other vaccines.
Insights
Neisseria meningitidis serogroup B lipopolysaccharide (LOS) and lipid A show adjuvant activity in mice, dependent on Toll-like receptor 4 (TLR4). Unglycosylated lipid A may be a candidate for vaccines.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Neisseria meningitidis serogroup B lipopolysaccharide (LOS) and its lipid A component are investigated for their immune-stimulating properties.
- Lipid A is a known Toll-like receptor 4 (TLR4) agonist, crucial for innate immune responses.
Purpose of the Study:
- To assess the adjuvant activity of meningococcal LOS and lipid A in different mouse models.
- To determine the role of TLR4 in the adjuvant effects of meningococcal LOS.
Main Methods:
- Evaluation of adjuvant activity of wild-type LOS, LOS mutants, and purified meningococcal lipid A in C3H/HeN and C3H/HeJ mice.
- Measurement of antibody titers (IgG subclasses) against outer membrane protein (OMP) and assessment of bactericidal activity of induced antibodies.
Main Results:
- Meningococcal lipid A and LOS demonstrated significant adjuvant activity in C3H/HeN mice, inducing high titers of IgG1, IgG2a, and IgG2b against OMP.
- Induced antibodies exhibited high bactericidal activity against serogroup B meningococci.
- Adjuvant activity was TLR4-dependent, as evidenced by the lack of response in C3H/HeJ mice.
Conclusions:
- Unglycosylated meningococcal lipid A retains adjuvant activity and may be a suitable candidate for Neisseria meningitidis serogroup B vaccines.
- The TLR4-dependent adjuvant properties of meningococcal lipid A suggest potential applications in other vaccine formulations.
Related Concept Videos
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