Lysophosphatidylcholine is a natural adjuvant that initiates cellular immune responses

Abstract

The discovery of new adjuvants that can stimulate the immune response to protein antigens is a major issue for the development of subunit vaccines. Lipoprotein oxidation occurring during the acute phase response (APR) to aggression of the organism, provide signals of danger that are detected by dendritic cells (DC). Among other instructive molecules generated during the APR, lysophosphatidylcholine (LPC) promotes mature DC generation from differentiating human monocytes in vitro. It is shown here that LPC also controls the initiation of an adaptive immune response in vivo. LPC displays adjuvant properties when injected to mice in mixture with various antigens. Immunizations with LPC induced the production of antigen-specific antibodies with an efficiency similar to Alum, the reference adjuvant for human vaccination.Importantly, LPC also induced cytotoxic T cell responses, opening perspectives for vaccine development. Therefore, LPC is a natural adjuvant for the immune system, inducing humoral and cellular immune responses.

Single Lysophosphatidylcholine Components Exhibit Adjuvant Activities In Vitro and In Vivo

“…A natural egg-derived mixture of LPC has been shown to promote mature DC generation in vitro and initiate adaptive immune responses in mice (6,15). The objective of this study was to determine which single molecular LPC component within the natural egg-derived LPC mixture is responsible for the adjuvant properties of this potential novel adjuvant that have been described.…”

“…Together, these data have identified LPC as a regulator of the efficient induction of phenotypic and functional DC maturation and have thus raised the possibility that LPC could be used as a vaccine adjuvant. Indeed, LPC can initiate both humoral and cellular responses against ovalbumin or egg lysozyme model antigens when it is injected subcutaneously (s.c.) into mice (15). One major concern that requires further evaluation of the value of LPC as an adjuvant is that the LPC used in those studies was a natural mixture extracted from chicken eggs.…”

Lysophospholipids of Different Classes Mobilize Neutrophil Secretory Vesicles and Induce Redundant Signaling through G2A

“…Neutrophils themselves express intracellular and secretory PLA 2 (64), raising the possibility of lyso-PL generation for autocrine or paracrine stimulation culminating through signaling via G2A. Although little is known of how and where lyso-PLs are stimulatory, the fact remains that lyso-PC and lyso-PS administered in vivo have been shown to have profound effects (7,(65)(66)(67). Furthermore, recent investigations linking loss of G2A to both atherosclerosis (20) and autoimmunity (68), and demonstrating the therapeutic use of lyso-PC in sepsis (7), underscore that a better understanding of lyso-PL stimulation is essential.…”

Selection of Adjuvants for Enhanced Vaccine Potency

“…Lysophosphatidylcholine (LPC) mixed with various antigens induced cytotoxic T cell responses and production of antigen-specific antibodies with an efficiency similar to Alum in mice [310]. Synthetic alkylglycerol analogues in a mixture with ovulbumin have been shown to increase anti-Ova IgG antibody production in sera of immunized mice and the relative levels of IgG1 and IgG2a depended on the carbon chain length [311].…”