Recent advances in lipopolysaccharide-based glycoconjugate vaccines

Abstract

Introduction:The public health burden caused by pathogenic Gram-negative bacteria is increasingly prominent due to antimicrobial resistance. The surface carbohydrates are potential antigens for vaccines against Gram-negative bacteria. The enhanced immunogenicity of the O-specific polysaccharide (O-SP) moiety of LPS when coupled to a carrier protein may protect against bacterial pathogens. However, because of the toxic lipid A moiety and relatively high costs of O-SP isolation, LPS has not been a popular vaccine antigen until recently. Areas covered: In this review, we discuss the rationales for developing LPS-based glycoconjugate vaccines, principles of glycoconjugate-induced immunity, and highlight the recent developments and challenges faced by LPS-based glycoconjugate vaccines. Expert opinion: Advances in LPS harvesting, LPS chemical synthesis, and newer carrier proteins in the past decade have propelled LPS-based glycoconjugate vaccines toward further development, through to clinical evaluation. The development of LPS-based glycoconjugates offers a new horizon for vaccine prevention of Gram-negative bacterial infection.

Immunisation with purified Coxiella burnetii phase I lipopolysaccharide confers partial protection in mice independently of co-administered adenovirus vectored vaccines

“…Five carrier proteins have been used in licensed glycoconjugate vaccines, including Haemophilus protein D, tetanus toxoid, diphtheria toxoid, cross-reactive material 197 (CRM197, a non-toxic mutant form of diphtheria toxoid), and serogroup B meningococcus outer membrane protein complex (OMPC) [ 55 ]. Conjugating sugar-based antigens to a carrier protein enables T cell help in inducing B cell affinity maturation, clonal expansion, and memory responses [ 56 ]. Capsular polysaccharides (CPS)-based glycoconjugates have been used in several licensed vaccines against Neisseria meningitidis, Haemophilus influenzae type b, and Streptococcus pneumoniae [ 57 ].…”

Immune response strategies of Brucella melitensis and their antigens in rats

“…The current study noted that TLR2 and TLR4 increase only in the group that is immunized with whole Sonicated Brucella melitensis which lose their ability to escape from innate immunity mechanisms. The lower antigenicity of Brucella smooth lipopolysaccharides (such as Brucella melitensis) to induce NOS-2 and COX-2 leads to lower activation ability of monocyte chemoattractant protein-1 (MCP-1) and macrophage-inflammatory protein that's lead to reduce the production of pro-inflammatory cytokines (23,24). The highly protective ability of REV1 in comparison with Sonicated antigen due to the ability of the REV1 vaccine to stimulate both humeral and cellular immune responses (25).…”

Glycans in HIV-1 vaccine design – engaging the shield

“…Indeed, a major breakthrough in generating anticarbohydrate IgG responses by vaccination came with the development of conjugate vaccines in which covalent linking of bacterial polysaccharide to carrier protein allowed activation of T cell help, leading to elicitation of antibody class switching, affinity maturation via somatic hypermutation (SHM) and selection, and memory [31]. This is exemplified by bacterial pathogens, such as Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, against which highly effective FDA-approved glycoconjugate-based vaccines have been developed [32].…”