Mucosal immunization with filamentous hemagglutinin protects against Bordetella pertussis respiratory infection

Abstract

Mucosal immunization of mice with purified BordeteUla pertussis filamentous hemagglutinin (FHA), by either the respiratory or the gut route, was found to protect against B. pertussis infection of the trachea and lungs. Intranasal immunization of BALB/c and (C57BL/6 x C3H/HeN)Fl adult female mice with FHA prior to B. pertussis aerosol challenge resulted in a 2 to 3 log reduction in number of bacteria recovered from the lungs and the tracheas of immunized mice in comparison to unimmunized controls. Intraduodenal immunization of adult mice with FEIA before infection also resulted in approximately a 2 log reduction in the recovery of bacteria from the lungs and the tracheas of immunized mice in comparison to unimmunized controls. Immunoglobulin A and immunoglobulin G anti-FHA were both detected in bronchoalveolar lavage fluids of mucosally immunized mice. Limiting dilution analysis revealed a 60-fold increase in the frequency of FHA-specific B cells isolated from the lungs of mice immunized intranasally with FHA in comparison to unimmunized control mice. These data suggest that both gut and respiratory mucosal immunization with a major adhesin ofB. pertussis generates a specific immune response in the respiratory tract that may serve as one means of mitigating subsequent B. pertussis respiratory infection.

Oral colonization and immune responses to Streptococcus gordonii expressing a pertussis toxin S1 fragment in mice

“…Sera and saliva were collected at day 0, weeks 4, 7, 8.5, 10, 13, 15 and 19. Bronchoalveolar lavage (BAL) £uids were collected at 19 week when the animals were euthanized [11].…”

Beta‐helix model for the filamentous haemagglutinin adhesin of Bordetella pertussis and related bacterial secretory proteins

“…FHA is one of the most efficiently secreted proteins of Gram-negative organisms, a property that may be exploited for secretion or surface display of passenger proteins (Renauld-Mongenie et al, 1996). In addition to its importance in bacterial adherence, FHA is a prominent immunogen (Kimura et al, 1990;Di Tommaso et al, 1991;Shahin et al, 1992). Acellular pertussis vaccines containing FHA have been in use since 1981 (Sato and Sato, 1984;Edwards, 1993).…”

The molecular basis for the virulence of bacterial pathogens: implications for oral vaccine development

“…In order to utilize the tac promoter it was not possible to regulate expression using the lac repressor as bacteria persisting in the host could not be induced using gratuitous inducers. The presence of the lac repressor drove expression down to such an extent that although the plasmid was stabilized no response against the heterologous protein was detected (Fairweather e t al., 1990). Thus the use of expression systems designed for routine laboratory use such as tac (Lac induction) or ; 1. pL (heat induction) are flawed in terms of their value for live vaccine development.…”

“…One approach is to move genes onto the bacterial chromosome (Hone e t al., 1988a; Strugnell e t a/., 1990). Obviously, because the genes are single copy, expression levels are driven down but it is still possible to obtain immune responses which can be protective in model systems, against the heterologous protein, for example the pertactin protein of Bordetella pertzkssis (Charles et al, 1988(Charles et al, , 1990bStrugnell e t al., 1992). Nakayama e t al.…”

“…Steven Chatheld in our group decided to monitor the behaviour of an S. t_yphimtlrizlm vaccine strain harbouring a plasmid driving expression of Fragment C from nirB. Earlier attempts to develop a single dose oral tetanus vaccine based on tac expression systems had met with partial success (Fairweather e t al., 1990). Unlike the experience with the tac promoter oral feeding of the hybrid vaccine strain to Balb/c mice resulted in almost perfect stability of the plasmid in bacteria recovered from the mice, even many days after inoculation.…”