Induction of mucosal immune responses against a heterologous antigen fused to filamentous hemagglutinin after intranasal immunization with recombinant Bordetella pertussis.

Abstract

Live vaccine vectors are usually very effective and generally elicit immune responses of higher magnitude and longer duration than nonliving vectors. Consequently, much attention has been turned to the engineering of oral pathogens for the delivery of foreign antigens to the gutassociated lymphoid tissues. However, no bacterial vector has yet been designed to specifically take advantage of the nasal route of mucosal vaccination. Herein we describe a genetic system for the expression of heterologous antigens fused to the filamentous hemagglutinin (FHA) in Bordetella pertussis. The Schistosoma mansoni glutathione S-transferase (Sm28GST) fused to FHA was detected at the cell surface and in the culture supernatants of recombinant B. pertussis. The mouse colonization capacity and autoagglutination of the recombinant microorganism were indistinguishable from those of the wildtype strain. In addition, and in contrast to the wild-type strain, a single intranasal administration of the recombinant strain induced both IgA and IgG antibodies against Sm28GST and against FHA in the bronchoalveolar lavage fluids. No anti-Sm28GST antibodies were detected in the serum, strongly suggesting that the observed immune response was of mucosal origin. This demonstrates, to our knowledge, for the first time that recombinant respiratory pathogens can induce mucosal immune responses against heterologous antigens, and this may constitute a first step toward the development of combined live vaccines administrable via the respiratory route.

Genetic Immunization with Lung-Targeting Macroaggregated Polyethyleneimine-Albumin Conjugates Elicits Combined Systemic and Mucosal Immune Responses

“…However, there was little systemic IgA response detected, as has been observed in some other immunization studies (64). The induction of secretory IgA in the lung is required for immunological protection in some model systems (65), but not in others (66).…”

Attenuated Bordetella pertussis Protects against Highly Pathogenic Influenza A Viruses by Dampening the Cytokine Storm

“…In addition, attenuated B. pertussis is particularly well adapted for the nasal delivery of heterologous vaccine antigens and represents an attractive mucosal vaccine delivery system (2,10,20,34,38,39). Constructing BPZE1 derivatives producing viral antigens, thereby combining anti-inflammatory properties with the ability to induce adaptive anti-influenza virus immune responses, may thus constitute an interesting strategy for future development.…”

Production ofNeisseria meningitidisTransferrin-Binding Protein B by RecombinantBordetella pertussis

“…Previous studies have shown that the highly efficient secretion mechanism of FHA can be used to present heterologous antigens by B. pertussis (38). Subsequently, we have found that a truncated derivative of FHA, named Fha44, that contains the N-proximal secretion determinants (16) was secreted even more efficiently than was full-length FHA (37).…”

“…However, efficacious mucosal vaccination generally requires multiple high-dose regimens (47). We have recently developed recombinant Bordetella pertussis strains able to induce mucosal (38) and systemic (33) antibody responses against heterologous antigens after a single i.n. administration.…”