Comparison of functional immune responses in humans after intranasal and intramuscular immunisations with outer membrane vesicle vaccines against group B meningococcal disease.
A serogroup B meningococcal outer membrane vesicle (OMV) vaccine was delivered either intranasally or intramuscularly to 12 and 10 volunteers, respectively. The mucosal vaccine was given as four weekly doses followed by a fifth dose after 5 months; each dose consisted of OMVs equivalent to 250 microg of protein. The intramuscular (i.m.) vaccine, consisting of the same OMVs but adsorbed to Al(OH)(3), was administered as three doses each of 25 microg of protein, with 6 weeks interval between first and second doses and the third dose after 10 months. Both groups of vaccinees demonstrated significant immune responses when measured as specific IgG antibodies against live meningococci, as serum bactericidal activity (SBA) and as opsonophagocytic activity. Two weeks after the last dose, the anti-meningococcal IgG concentrations were significantly higher in the i.m. group (median IgG concentration: 43.1 microg/ml) than in the intranasal group (10.6 microg/ml) (P=0.001). The corresponding opsonophagocytic activity was 7.0 and 3.0 (median log(2) titre) (P=0.001), and the SBA was 5.0 and 2.0 (median log(2) titre) (P=0.005), for the i.m. and intranasal groups, respectively. The last immunisation induced an enhanced immune response in the i.m. group, whereas the intranasal group showed no significant booster response. Accordingly, affinity maturation of anti-OMV-specific IgG antibodies was seen only after i.m. vaccination. The IgG1 subclass dominated the responses in both groups, whereas the significant IgG3 responses observed in the i.m. group were absent in the intranasal group. Although the intranasal OMV vaccination schedule used here induced functional immune responses relevant to protection, an improved vaccine formulation and/or a modified mucosal immunisation regimen may be needed to achieve a systemic effect comparable to that seen after three doses of intramuscular vaccination.
Aase
A
A
Division of Infectious Disease Control, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, NO-0403 Oslo, Norway. audun.aase@fhi.no
Naess
L M
LM
Sandin
R H
RH
Herstad
T K
TK
Oftung
F
F
Holst
J
J
Haugen
I L
IL
Høiby
E A
EA
Michaelsen
T E
TE
D000281:Administration, Intranasal; D000907:Antibodies, Bacterial / Q000097:blood; D005434:Flow Cytometry; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D008585:Meningitis, Meningococcal / Q000276:immunology*; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D010587:Phagocytosis; D016897:Respiratory Burst; D015610:Serum Bactericidal Test
D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines