TY - JOUR
T1 - Intranasal immunization of mice with recombinant Streptococcus gordonii expressing NadA of Neisseria meningitidis induces systemic bactericidal antibodies and local IgA
AU - Ciabattini, Annalisa
AU - Giomarelli, Barbara
AU - Parigi, Riccardo
AU - Chiavolini, Damiana
AU - Pettini, Elena
AU - Aricò, Beatrice
AU - Giuliani, Marzia M.
AU - Santini, Laura
AU - Medaglini, Donata
AU - Pozzi, Gianni
N1 - Funding Information:
This study has been carried out with the financial support from the Commission of the European Communities, Sixth Framework Programme, contract LSHP-CT-2003-503240, “Mucosal Vaccines for Poverty-Related Diseases” (MUVAPRED); Fifth Framework Programme, contract QLK2-CT-1999-00228, “Mucosal Immunization and Vaccine Development” (MUCIMM); MIUR (FIRB RBNE01RB9B_009 and FIRB RBNE01N9EE) and a generous grant from the Dormeur Foundation.
PY - 2008/8/5
Y1 - 2008/8/5
N2 - NadA and NhhA, two surface proteins of serogroup B Neisseria meningitidis identified as candidate vaccine antigens, were expressed on the surface of the human oral commensal bacterium Streptococcus gordonii. Recombinant strains were used to immunize BALB/c mice by the intranasal route and the local and systemic immune response was assessed. Mice were inoculated with recombinant bacteria administered alone or with LTR72, a partially inactivated mutant of Escherichia coli heat-labile enterotoxin, as a mucosal adjuvant. Intranasal immunization with live bacteria expressing NadA induced a significant serum antibody response, with a prevalence of the IgG2a subclass, bactericidal activity in the sera of 71% of animals, and a NadA-specific IgA response in nasal and bronchoalveolar lavages. A formalin-inactivated recombinant strain of S. gordonii expressing NadA was also administered intranasally, inducing a systemic and mucosal humoral response comparable to that of live bacteria. The administration of recombinant bacteria with the mucosal adjuvant LTR72 stimulated a stronger systemic antibody response, protective in 85% of sera, while did not increase the local IgA response. Recombinant S. gordonii expressing NhhA induced a systemic but not mucosal antibody response. These data support the role of NadA as vaccine candidate against serogroup B meningococci, and the use of S. gordonii as vector for intranasal vaccination.
AB - NadA and NhhA, two surface proteins of serogroup B Neisseria meningitidis identified as candidate vaccine antigens, were expressed on the surface of the human oral commensal bacterium Streptococcus gordonii. Recombinant strains were used to immunize BALB/c mice by the intranasal route and the local and systemic immune response was assessed. Mice were inoculated with recombinant bacteria administered alone or with LTR72, a partially inactivated mutant of Escherichia coli heat-labile enterotoxin, as a mucosal adjuvant. Intranasal immunization with live bacteria expressing NadA induced a significant serum antibody response, with a prevalence of the IgG2a subclass, bactericidal activity in the sera of 71% of animals, and a NadA-specific IgA response in nasal and bronchoalveolar lavages. A formalin-inactivated recombinant strain of S. gordonii expressing NadA was also administered intranasally, inducing a systemic and mucosal humoral response comparable to that of live bacteria. The administration of recombinant bacteria with the mucosal adjuvant LTR72 stimulated a stronger systemic antibody response, protective in 85% of sera, while did not increase the local IgA response. Recombinant S. gordonii expressing NhhA induced a systemic but not mucosal antibody response. These data support the role of NadA as vaccine candidate against serogroup B meningococci, and the use of S. gordonii as vector for intranasal vaccination.
KW - Mucosal vaccines
KW - Protection
KW - Recombinant bacteria
UR - http://www.scopus.com/inward/record.url?scp=47149091261&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=47149091261&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2008.05.049
DO - 10.1016/j.vaccine.2008.05.049
M3 - Article
C2 - 18582996
AN - SCOPUS:47149091261
SN - 0264-410X
VL - 26
SP - 4244
EP - 4250
JO - Vaccine
JF - Vaccine
IS - 33
ER -