Oral and rectal immunization of adult female volunteers with a recombinant attenuated Salmonella typhi vaccine strain

Abstract

An attenuated strain of Salmonella typhi ⌬cya ⌬(crp-cdt) ⌬asd expressing a gene encoding a hepatitis B virus core-pre-S protein was tested in female adult volunteers for its ability to elicit a systemic and a mucosal immune response. Specifically, our purpose was to evaluate the potential of such a vaccine strain to induce specific secretory immunoglobulin A (sIgA) at genital and rectal surfaces. Oral and rectal routes of immunization were compared: oral immunization induced seroconversion against the bacterial lipopolysaccharide (LPS) in six out of seven volunteers, while after rectal immunization only one out of six volunteers seroconverted against LPS. To our disappointment, the latter volunteer was also the only one who seroconverted against the carried antigen (pre-S1), demonstrating the poor ability of this live vaccine to induce an immune response against the carried antigen. Anti-LPS sIgA was found in both the vaginal and cervical secretions of a volunteer who presented a strong seroconversion after oral immunization (16-fold increase in anti-LPS IgG). Smaller amounts of anti-LPS sIgA were found in the rectal secretions of one orally and one rectally immunized volunteer and in the saliva of three orally and one rectally immunized woman. Our data show for the first time that it is possible to induce specific sIgA in the genital and rectal tracts of women by using an S. typhi vaccine strain.

vaccines for use in humans: present and future perspectives

“…In two volunteer studies, S. enterica var. Typhi M4073 expressing hepatitis B antigens (using the asd balancedlethal system) has been evaluated [59,71]. In both studies the vaccine was poorly immunogenic against the heterologous antigen and, following oral inoculation, caused occasional febrile reactions.…”

“…Ultimately even bacteria which had lost the antigen-encoding plasmid were able to survive, possibly as a result of mutations spontaneously occurring in hok [114]. Plasmid stabilisation systems in Salmonella have been used with some success in human vaccine trials [71,91,115,116].…”

Probiotics: multifarious oral vaccine against infectious traumas

“…Derivatives of both pathogenic and nonpathogenic bacteria can be used as live vaccines. These include Salmonella typhi, Shigella flexineri, Listeria monocytogenes, V. cholerae and Escherichia coli as well as some nonpathogenic bacteria such as Lactobacillus and Bifidobacterium (McGhee et al, 1992;Klijn et al, 1995;Nardelli-Haefliger et al, 1996).…”

Recombinant live Salmonella spp. for human vaccination against heterologous pathogens

“…No seroresponse to this heterologous antigen was elicited in humans after a single oral dose in a study at the Center for Vaccine Development in Baltimore, MD, USA [46]. A similar study using the same vaccine was performed at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, with the exception that the vaccine was applied in three doses, spaced by several weeks, and was given orally or rectally to female volunteers only [48]. Out of six rectally immunised volunteers, only one seroconverted against the pre-S1 antigen.…”

“…In another balanced^lethal system, thymidine requirement caused by a mutation in the chromosomal thymidylate synthetase (thyA) gene is complemented by a plasmid carrying a functional thyA gene [58]. Both systems allow for a stable, high expression of foreign antigens in recombinant Salmonella strains and have been used with some success in human vaccine trials [38,40,46,48]. In addition, both systems provide the additional advantage that no antibiotic resistance marker is required for the selection of transformed bacteria.…”