Carrier‐mediated enhancement of cognate T cell help: the basis for enhanced immunogenicity of meningococcal outer membrane protein polysaccharide conjugate vaccine

• Published in: European journal of immunology 2001-08, Vol.31 (8), p.2373-2381
• Main Authors: Pérez‐Melgosa, Mercedes, Ochs, Hans D., Linsley, Peter S., Laman, Jon D., Meurs, Marjan van, Flavell, Richard A., Ernst, Robert K., Miller, Samuel I., Wilson, Christopher B.
• Format: Article
• Language: English
• Subjects: Adjuvant; Adjuvants, Immunologic; Adult; Animals; Antigens, CD - metabolism; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B7-2 Antigen; Bacterial Outer Membrane Proteins - administration & dosage; Bacterial Outer Membrane Proteins - immunology; Carrier; Cells, Cultured; Cytokines - biosynthesis; Cytokines - genetics; Flow Cytometry; Haemophilus influenzae; Haemophilus Vaccines - immunology; Humans; Immunohistochemistry; Infant, Newborn; Killer Cells, Natural - immunology; Lymphocyte Activation; Membrane Glycoproteins - metabolism; Meningococcal Vaccines - administration & dosage; Meningococcal Vaccines - immunology; Mice; Mice, Inbred Strains; Monocytes - immunology; Neisseria meningitidis; Neisseria meningitidis - immunology; polysaccharides; Polysaccharides, Bacterial - administration & dosage; Polysaccharides, Bacterial - immunology; T-Lymphocytes, Helper-Inducer - immunology; Tetanus Toxoid - immunology; Up-Regulation; Vaccine; Vaccines, Conjugate - administration & dosage; Vaccines, Conjugate - immunology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/1521-4141(200108)31:8<2373::AID-IMMU2373>3.0.CO;2-G

Haemophilus influenzae type b capsular polysaccharide (PRP) conjugate vaccines, which are thought to induce T cell‐dependent antibody production, induce protective responses after a single dose in individuals under 15 months of age. However, multiple doses of these vaccines are required to induce protective antibody responses in infants, with the exception of PRP conjugated to meningococcal outer membrane proteins (OMPC), which does so after a single dose. The basis for this difference is not fully understood, although others have proposed that OMPC and porins, the major protein component of OMPC, act as adjuvants or mitogens. In this report OMPC is shown to enhance CD40 ligand‐mediated, T cell‐dependent antibody production in mice. This paralleled the induction by OMPC of CD86, CD80 and CD40 costimulatory molecules on human neonatal and murine B cells and of Th1 cytokines. Neither porins nor lipopolysaccharide fully reproduced the effects of OMPC. These studies indicate that OMPC acts both as carrier and adjuvant, and thereby enhances T cell‐dependent antibody responses in human infants.