Expression of human CEACAM1 in transgenic mice limits the Opa-specific immune response against meningococcal outer membrane vesicles.
Outer membrane vesicles (OMVs) have been extensively investigated as meningococcal vaccine candidates. Among their major components are the opacity (Opa) proteins, a family of surface-exposed outer membrane proteins important for bacterial adherence and entry into host cells. Many Opa-dependent interactions are mediated through the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family of receptors. Importantly, binding of Opa to CEACAM1 has been reported to suppress human CD4 T cell proliferation in vitro in response to OMV preparations. This raises the question whether OMV vaccines should contain Opa proteins at all. Until now it has been difficult to answer this question, as the proposed immunosuppressive effect was only demonstrated with human cells in vitro, while immunization experiments in mice are not informative because the Opa interaction is specific for human CEACAM1. In the present study we have used Opa+ and Opa- OMVs for immunization experiments in a human CEACAM1 transgenic mouse model. OMVs were prepared from a meningococcal strain H44/76 variant expressing the CEACAM1-binding OpaJ protein, and from an isogenic variant in which all opa genes have been inactivated. Both the CEACAM1 expressing transgenic mice and their congenic littermates lacking it were immunized twice with the OMV preparations, and the sera were analyzed for bactericidal activity and ELISA antibody titres. Total IgG antibodies against the OMVs were similar in both mouse strains. Yet the titres for IgG antibodies specific for purified OpaJ protein were significantly lower in the mice expressing human CEACAM1 than in the nontransgenic mice. No significant differences were found in bactericidal titres among the four groups. Overall, these data indicate that expression of human CEACAM1 confers a reduced Opa-specific antibody response in vivo without affecting the overall immune response against other OMV antigens.
Institute for Translational Vaccinology (InTraVacc), Antonie van Leeuwenhoeklaan 9, 3720 AL Bilthoven, The Netherlands; Department of Infectious Diseases and Immunology, Utrecht University, 3584 CL Utrecht, The Netherlands. Electronic address: Afshin.Zariri@intravacc.nl.
Afshin
A
Zariri
Harry
H
van Dijken
Hendrik-Jan
HJ
Hamstra
Michiel
M
van der Flier
Gestur
G
Vidarsson
Jos P M
JP
van Putten
Claire J P
CJ
Boog
Germie
G
van den Dobbelsteen
Peter
P
van der Ley
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001770:Blood Bactericidal Activity; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D055252:Cell-Derived Microparticles / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014611:Vaccination / Q000379:methods*
D000907:Antibodies, Bacterial; D015703:Antigens, CD; D001425:Bacterial Outer Membrane Proteins; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines; C090348:Opa protein, Neisseria
CEACAM1; Meningococcal vaccine; Neisseria meningitidis; OMV; Opa; Opacity proteins; Outer membrane vesicles