A conjugate vaccine composed of a heat shock protein 60 T-cell epitope peptide (p458) and Neisseria meningitidis type B capsular polysaccharide

Pneumococcal Capsular Polysaccharide Is Immunogenic When Present on the Surface of Macrophages and Dendritic Cells: TLR4 Signaling Induced by a Conjugate Vaccine or by Lipopolysaccharide Is Conducive

“…Protection was associated with PS4-specific IgG Ab in most but not in all the mice, a T cell response to the p458 carrier and long-term memory. Vaccines composed of p458 conjugated to the CPS molecules of S. pneumoniae, Salmonella (16), or meningococcus B and C (17) were also immunogenic, even when injected in PBS without an added adjuvant. These findings suggested that CPS p458 conjugates might act as adjuvants, as well as specific immunogens.…”

Biomarker vaccines

“…We have used a peptide of self-HSP60, termed p458, to formulate subunit vaccines by conjugating p458 to various pathogen virulence molecules such as the capsular polysaccharides (CPS) of Salmonella, 21 Pneumococcus 22 or Meningococcus types C and B. 23 Some bacterial HSP60 peptides too are agonists for effective innate receptors, and can also serve in effective conjugate vaccines; the phenomenon is not limited to self. 21 We have also linked HSP60 peptide p458 to peptide epitopes of West Nile Virus (in preparation) and murine CMV.…”

“…1). Note that these conjugate vaccines are effective without the need for added adjuvant, [21][22][23] a factor that adds to safety. The detailed results can be seen in the publications.…”

“…(1) The self-HSP60 peptide conjugate can be more effective in generating T-dependent antibodies and memory than foreign carrier molecules and can increase resistance to lethal challenge by a million-fold-exemplified in a Pneumococcal vaccine; 22 (2) The self-HSP60 peptide conjugate can convert non-immunogenic or very poorly immunogenic pathogen molecules into strong immunogens-exemplified in a vaccine to Meningococcus B; 23 (3) The self-HSP60 peptide conjugate can induce immune memory and cytoxic T cells that abrogate the persistence of a pathogen in a naturally protected site-exemplified by the eradication of murine CMV from its hideout in the salivary glands. 24 Immunization with the virus itself could not induce the mouse to clear CMV from its salivary glands; the conjugate virus-host biomarker vaccine was successful.…”

A Novel Linker Methodology for the Synthesis of Tailored Conjugate Vaccines Composed of Complex Carbohydrate Antigens and Specific TH‐Cell Peptide Epitopes

“…This heptadecapeptide representing a strongly immunogenic T-cell epitope of hsp60 between residues 458 and 472 (p458m) has been shown to serve as a potent carrier in conjugate vaccines against infections with S. pneumoniae and N. meningitidis. [11,35,36] The p458m epitope was assembled in an automated synthesizer using Fmoc strategy [37] starting from Rapp Tentagel R resin [38] 7 equipped with Fmoc-isoleucine via the acid-labile Wang linker [39] and employing a combination of HBTU/ HOBt [40] for activation. After completion of the peptide sequence, S-trityl protected mercaptopropionic acid 8, which is readily available from mercaptopropionic acid and triphenylmethanol, was coupled to install a sulfhydryl moiety on the peptide to serve as attachment point for the linker (Scheme 3).…”