Summary auto-generated
Researchers administered a whole-cell Bordetella pertussis vaccine intranasally to six healthy adult volunteers in four weekly doses (250 μg protein each). All participants developed increased nasal IgA antibodies to pertussis whole-cell antigen, with peak responses reaching seven-fold above baseline. Three vaccinees with high nasal responses also developed systemic IgA and IgG antibodies. The vaccine had negligible effects on antibody responses to pertussis toxin and only modest effects on filamentous hemagglutinin antibodies. Strikingly, all vaccinees developed significant cross-reactive IgA antibody responses to meningococcal outer-membrane vesicle antigens in nasal and salivary secretions, despite no detectable systemic responses to meningococcal antigens. The vaccine was well-tolerated with no adverse effects observed. These findings suggest that intranasal immunization with particulate bacterial antigens without adjuvants can effectively induce mucosal immune responses and may generate broader specificities in secretory antibodies than achievable through systemic responses alone.
Key findings
- Intranasal whole-cell pertussis vaccine induced significant IgA antibody responses in nasal secretions in all six vaccinees, with peak levels seven-fold above baseline
- Three vaccinees developed simultaneous systemic (serum) IgA and IgG antibody responses, indicating the vaccine stimulated both mucosal and systemic immunity
- Unexpectedly, all vaccinees developed cross-reactive IgA antibodies against meningococcal outer-membrane antigens in nasal and salivary secretions, but not in serum, suggesting mucosal immunization induces broader antibody specificities
- The vaccine was well-tolerated with no adverse clinical effects or markers of inflammation
- Responses to specific pertussis antigens (pertussis toxin and filamentous hemagglutinin) were weak or absent despite strong responses to whole-cell antigen
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Abstract
A whole-cell pertussis vaccine, each dose consisting of 250 µg of protein, was given intranasally four times at weekly intervals to six adult volunteers. All vaccinees responded with increases in nasal fluid IgA antibodies to Bordetella pertussis whole-cell antigen. Three vaccinees with high nasal antibody responses also developed increased serum IgA and IgG antibodies to this antigen. Salivary antibody responses to the whole-cell antigen, as well as antibodies in serum and secretions to pertussis toxin (PT) and filamentous haemagglutinin (FHA) were negligible, except for a moderate increase in nasal fluid antibodies to FHA. Unexpectedly, the same vaccinees developed significant rises in nasal and salivary IgA antibodies to meningococcal outer-membrane antigens, whereas corresponding serum IgA and IgG antibodies were unchanged. Thus it appears that mucosal immunisation may induce secretory antibodies with broader specificities than can be found in serum.