Lipopolysaccharide

Creative Biolabs is a world leader in the field of vaccine adjuvants development. With our extensive experience and advanced platform, we are therefore confident in offering the best services for vaccine adjuvants for use in vaccine development and guarantee the finest results for our customers all over the world.

Vaccine Adjuvant - Creative Biolabs

Lipopolysaccharide

Lipopolysaccharide (LPS) is a major component of the Gram-negative bacterial cell wall from Salmonella minnesota R595, which has long been known as a powerful immunomodulator. It is localized in the outer layer of the membrane and exposed on the cell surface in the non-capsulated strains. LPS is a large molecule which consists of a lipid and a polysaccharide composed of O-antigen, outer core and inner core joined by a covalent bond, contributing greatly to the structural integrity of the bacteria, and protecting the membrane from certain kinds of chemical attack. Its low-toxicity derivative monophosphoryl lipid A (MPLA) is a TLR4 agonist and can induce a strong Th1 response which has been used widely in clinical trials as a component in prophylactic and therapeutic vaccines targeting infectious disease, cancer and allergies. Therefore, MPLA had a similar adjuvant effect on vaccine development.

Monophosphoryl Lipid A

Structure of Monophosphoryl Lipid A

Monophosphoryl lipid A (MPLA) is an endotoxin derivative of LPS, a promising adjuvant candidate for a number of human vaccines and has been shown to be safe, well-tolerated, and effectively enhance immune responses to co-administered vaccine antigens. MPLA is produced by hydrolysis of native diphosphoryl lipid A, the component of LPS that is recognized by TLR4, resulting in the removal of all but a single phosphate group and various degrees of deacylation. These structural alterations decrease systemic toxicity by >99% compared to native lipid A, resulting in an immunomodulatory agent with greater potential for clinical use. The attenuated toxicity of MPLA is associated with reduced induction of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and gamma interferon (IFN-γ) during initial exposure. MPLA retains significant immunomodulatory activity and prior treatment with MPLA increases survival after otherwise lethal exposure to LPS in animal models.

The Prospect of MPL Adjuvant

MPL is suitable as an adjuvant for human vaccine formulations with notable immunostimulatory activity and greater Th1 than Th2 stimulating potential. MPL adjuvant has been administered to more than 12,000 humans and has proven to be both safe and effective in a variety of clinical contexts. Used in combination with antigen, MPL adjuvant alone, or combined with other adjuvants has been shown to augment humoral and cell-mediated immune responses. The corresponding increase in geometric mean titers and rate of seroconversion/ seroprotection in the hepatitis B vaccine augmented with MPL adjuvant has reduced the dosing requirement compared to the alum-based vaccine. The ability of MPL adjuvant to enhance cellular immune responses including CTL responses highlight the utility of this adjuvant in cancer vaccines. MPL enhances the immune response via the production of a wide array of pro-inflammatory cytokines and chemokines through the signal of TLR4. The excellent safety profile and extensive clinical experience highlight broad applicability for MPL adjuvant in a wide variety of vaccine strategies.

Creative Biolabs is a leader in the field of vaccine adjuvant development and has focused on the lipopolysaccharide and its derivative monophosphoryl lipid A for many years. We have experts who are able to help you with the development of the lipopolysaccharide or monophosphoryl lipid A for use in vaccines. If you are interested in our services, please contact us for more details.

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Reference

  1. Paul Baldrick. (2002). “Safety evaluation of monophosphoryl lipid A (MPL): an immunostimulatory adjuvant” Regulatory Toxicology and Pharmacology, 35, 398-410.

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