Table 1.
Main characteristics of mucosal vaccines against pertussis.
| Vaccine type | Model | Route | Immune response | Protection | Ref | ||
|---|---|---|---|---|---|---|---|
| Non-replicating vaccines | Inactivated whole-cell vaccines (n=7) | ||||||
| wPV* | Human | Aerosol | Specific mucosal IgA; no serum IgG | ND | (12) | ||
| wPV | Human | Oral | Agglutinating salivary antibodies; low specific IgG in sera; cellular responses | Lower disease incidence the first year following immunization | (13) | ||
| wPV | Human | Nasal | Specific mucosal responses in the nasal fluids (neglectable in the saliva); substantial serum antibodies | ND | (14) | ||
| wPV + CT | Human | Nasal or rectal | Low systemic or mucosal responses following rectal immunization Specific IgA and IgG in serum, saliva and feces following nasal administration |
Against nasopharyngeal colonization | (15) | ||
| DTwP | Mouse | Oral | Specific serum IgG and IgA in saliva and intestinal secretion | ND | (16) | ||
| wPV | Human | Nasal | Systemic cellular responses (Th1-type) | (17) | |||
| wPV + curdlan | Mouse | Nasal | Th17 cells in the spleen; reduction of pro-inflammatory responses | Against colonization in the upper and lower respiratory tract; reduced leukocytosis | (18) | ||
| Acellular vaccines + mucosal adjuvants (n=12) | |||||||
| aPV + LT | Mouse | Nasal | Th1 and Th2 cells in the spleen and lymph nodes; local and systemic specific antibody responses | Against lung colonization | (19) | ||
| DTwP or PRN + LT | Neonatal mice | Nasal | T- and B-cell responses, poor serum antibody production | Against lung colonization | (20) | ||
| PRN or FHA | Mouse | Nasal | Low antibody-secreting cells in lungs but strong priming | Against lung colonization | (21) | ||
| PT and FHA + CTB | Mouse | Nasal | Specific systemic antibody responses; no mucosal antibodies | Against lung colonization | (22) | ||
| PT + CTB | Mouse | Nasal | Mucosal IgA and systemic antibodies with anti-PT activity | Against lung colonization | (23) | ||
| Fim2 + CTB | Mouse | Nasal | Th1 and Th2 cells; specific serum IgG and specific IgG and IgA in bronchoalveolar lavages | Against lung colonization | (24) | ||
| DTwP + onjisaponin | Mouse | Nasal | Specific antibodies in the serum and in nasal washes | ND | (25) | ||
| PT, FHA, PRN + BLP | Mouse | Nasal | Anti-PT and anti-FHA in the nasal washes | Against lung colonization | (26) | ||
| DTaP + curdlan | Mouse | Nasal | Anti-PT and anti-FHA IgG in serum and lung IgA; Th17 response and neutrophilia; reduction of pulmonary pro-inflammatory cytokines | Against colonization of the upper and lower respiratory tract | (27) | ||
| aPV + curdlan | Mouse | Nasal | Long-lasting serum and lung antibodies | Long-lasting against colonization in lower and upper respiratory tract; reduced inflammation | (28) | ||
| PT, FHA, Prn + CpG ± alum | Mouse | Nasal | Specific antibodies in the serum and in the lungs; Th1 profile and activation of macrophages | Against lung colonization | (29) | ||
| aPV + LP-GMP | Mouse | Nasal | Th17 response and memory T cells, reduction of Th2 responses | Long-lasting protection against nasal colonization | (30) | ||
| Acellular vaccines in particulate formulations (n=7) | |||||||
| LPS or outer membrane proteins + liposomes | Mouse | Oral or nasal | Short-lived antibodies in lung washes; specific IgG, no IgA | ND | (31) | ||
| PT in poly[di(sodium carboxylatophenoxy)phosphazene] microparticles | Mouse | Nasal | Specific systemic and mucosal antibodies; long-term systemic, lung and nasal memory B cells; mixed Th1/Th2 responses | Against lung colonization | (32) | ||
| FHA, PT or PRN in poly-lactide-co-glycolide microspheres | Mouse | Nasal | Specific antibodies in the serum and in bronchoalveolar lavages | Against lung colonization | (33) | ||
| FHA + PT in poly-lactide-co-glycolide microspheres | Mouse | Oral | Specific serum and mucosal antibodies; specific Th1 and Th2 responses | Against lung colonization | (34) | ||
| Fimbria in poly-lactide-co-glycolide microsphere | Mouse | Oral | Specific systemic and local antibodies | Against colonization of the lungs and the trachea | (35) | ||
| FHA + PT with N-trimethyl chitosan nanoparticles | Mouse | Nasal | Anti-PT and anti-FHA IgG and IgA in sera and nasal washes, respectively; Th2, Th1 and Th17 cellular responses | ND | (36) | ||
| FHA + PT in chitosan | Mouse | Nasal | Enhanced anti-PT and anti-FHA antibodies in the nasal washes and anti-FHA IgG in serum | ND | (37) | ||
| OMV (n=5) | |||||||
| OMV | Mouse | Nasal | Inflammatory chemokine CCL-20 and IL-6 and TNF-α cytokines in the first hours post-immunization | Against lung colonization | (38) | ||
| OMV | Mouse | Nasal | Specific mucosal and systemic antibodies; memory B cells in lungs and spleen; Th1 and Th17 responses in lung and mixed Th1, Th2 and Th17 responses in the spleen | Against colonization of the upper and lower respiratory tract | (39) | ||
| OMVBpPagL | Mouse | Nasal | Reduction of inflammatory cytokines IL-6 and IL-1β | Against lung colonization | (40) | ||
| OMV | Mouse | Pulmonary | Mucosal IgA and systemic IgG and IgG-secreting memory B cells; Th17 cells and reduction of Th2 cytokines and of IL-10 in serum | Against colonization of the upper and lower respiratory tract | (41) | ||
| Spray-dried OMV | Mouse | Pulmonary | Mucosal IgA; broad systemic IgG; mixed Th1/Th17 responses | Against colonization in lower and upper respiratory tract | (42) | ||
| Replicating vaccines | Recombinant vaccines (n=10) | ||||||
| S. dublin ΔaroA + FHA | Mouse | Oral | Anti-FHA IgA in serum and gut washes; short-lived antibody responses | ND | (43) | ||
| S. typhimurium ΔaroAΔaroD + PRN | Mouse | Oral | Specific Th1-type response; no specific antibodies | ND | (44) | ||
| S. typhimurium ΔaroA + FHA or E. coli + FHA | Mouse | Oral | Specific serum IgG + IgG and IgA in the lungs | ND | (45) | ||
| S. typhimurium ΔaroA + PTS1, S. typhimurium Ty21a + PTS1 or E. coli + PTS1 | Mouse | Oral | Specific serum IgG + IgG and IgA in the lungs | ND | (46) | ||
| S. typhimurium ΔaroA + PT-S1-S5 | Mouse | Oral | Specific serum IgG | No protection against intracerebral challenge | (47) | ||
| S. typhi CVD 908 + PTS1 | Mouse | Oral or Nasal | Neutralizing anti-PT antibodies after nasal vaccination | ND | (48) | ||
| V. cholerae IEM101 + Tcf | Mouse | Nasal | No detectable antibodies | Against tracheal, but not lung colonization | (49) | ||
| L. lactis + PTS1 + FHA type I immunodominant domain | Mouse | Oral and nasal | Specific serum IgG; specific IgA in lung and feces; nasal immunization induces a strong Th1 response | ND | (50) | ||
| S. gordonii + PTS1 | Mouse | Oral | Specific IgA in saliva; no serum antibodies | ND | (51) | ||
| S. mutans + PTS1 | Mouse | Oral | Specific mucosal IgA | Against lung colonization | (52) | ||
| Live attenuated Bordetella strains (n=22) | |||||||
| B. bronchiseptica lacking ACT and the type III secretion system | Mouse | Nasal | Induction of Th1 response and reduction of IL-10 compared to the parental strain | Against colonization of the lower respiratory tract; reduced lung pathology | (53) | ||
| B. bronchiseptica lacking ACT, FHA, PRN, Fim and BipA | Mouse | Nasal | Low serum antibody titers | Against colonization of the upper and lower respiratory tract; reduced lung pathology | (54) | ||
| B. pertussis ΔaroA | Mouse | Respiratory | Serum IgG and IgGA | Against lung colonization | (55) | ||
| B. pertussis ΔaroQ | Mouse | Nasal | Humoral and cellular responses (Th1 and Th2) | Against lung colonization | (56) | ||
| B. pertussis Δptx | Mouse | Nasal | Serum IgG against FHA | Against lung colonization | (57) | ||
| B. pertussis Δptx | Mouse | Nasal | Specific genital IgA and IgG | ND | (58) | ||
| B. pertussis BPZE1 | Adult and infant mice | Nasal | Antigen-specific antibodies and Th1 responses | Against lung colonization; reduced lung inflammation | (59) | ||
| B. pertussis BPZE1 | Mouse | Nasal | Dose-dependent antigen-specific serum antibodies, specific IgG and IgA in bronchoalveolar lavage fluids Dose-dependent Th1 responses |
Against lung colonization in a dose-dependent manner; reduced lung inflammation | (60) | ||
| B. pertussis BPZE1 | Mouse | Nasal | Long-term specific serum IgG; IFN-γ-producing T cells | Against lung colonization | (61) | ||
| B. pertussis BPZE1 | Mouse | Aerosol | Long-lasting serum antibodies | Long-lasting against lung colonization | (62) | ||
| B. pertussis BPZE1 | Mouse | Nasal | IL-10, IL-17, IFN-γ and IL-2 following stimulation with FHA; induction of IL-17 and IFN-γ following stimulation with PTX | Against lung colonization | (63) | ||
| B. pertussis BPZE1 | Mouse | Nasal | IL-17-dependent secretory IgA in nasal washes and Th17 and Th1 TRM cells in the nose | Against colonization of the lower and upper respiratory tract. | (64) | ||
| B. pertussis BPZE1 | Mouse | Nasal | Maintenance of Th1/Th17 responses after aPV boosting | Against lung colonization | (65) | ||
| B. pertussis BPZE1 | Adult and neonatal mice | Aerosol | Specific IgG2a and Th1 responses | Against lung inflammatory pathology | (66) | ||
| B. pertussis BPZE1 | Mouse | Nasal | ND | Early protection against lung colonization | (67) | ||
| B. pertussis BPZE1 | Baboon | Tracheal and nasal | Specific serum IgG and IgA | Against nasopharyngeal colonization; against leukocytosis | (68) | ||
| B. pertussis BPZE1 | Human | Nasal | Specific serum IgG | ND | (69) | ||
| B. pertussis BPZE1 | Human | Nasal | Specific serum IgG and IgA | ND | (70) | ||
| B. pertussis BPZE1 | Human | Nasal | Specific B cell responses | ND | (71) | ||
| B. pertussis BPZE1 | Human | Nasal | Specific T cell responses and broad serum antibody responses | ND | (72) | ||
| B. pertussis BPZE1 | Mouse | Nasal | Specific serum IgG | Against colonization in lower and upper respiratory tract in the presence of pre-existing anti-PRN antibodies | (73) | ||
| B. pertussis BPZE1 | Mouse | Nasal | Anti-Fim2 and anti-Fim3 serum antibodies | Against lung colonization by Fim3 only producing B. pertussis | (74) | ||
ACT, adenylate cyclase toxin; aPV, acellular pertussis vaccine; BLP, bacterium-like particles; CT, cholera toxin; CTB, cholera toxin B subunit; DTaP, diphtheria-tetanus-acellular pertussis vaccine; DTwP, diphtheria-tetanus-whole-cell pertussis vaccine; wPV, whole-cell pertussis vaccine; FHA, filamentous haemagglutinin; Fim, fimbriae; LPS, lipopolysaccharide; LT, E. coli heat labile toxin; ND, not determined; OMV, outer membrane vesicles; OMV BpPagL, outer membrane vesicle from recombinant B. pertussis producing PagL; PRN, pertactin; PT, pertussis toxin; PTS1, pertussis toxin S1 subunit; Tcf, tracheal colonization factor; TRM, tissue-resident memory T cells.