Abstract
An attenuated strain of Salmonella typhi delta(cya) delta(crp-cdt) delta(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.
Full Text
The Full Text of this article is available as a PDF (204.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bao J. X., Clements J. D. Prior immunologic experience potentiates the subsequent antibody response when Salmonella strains are used as vaccine carriers. Infect Immun. 1991 Oct;59(10):3841–3845. doi: 10.1128/iai.59.10.3841-3845.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bartholomeusz R. C., Forrest B. D., Labrooy J. T., Ey P. L., Pyle D., Shearman D. J., Rowley D. The serum polymeric IgA antibody response to typhoid vaccination; its relationship to the intestinal IgA response. Immunology. 1990 Feb;69(2):190–194. [PMC free article] [PubMed] [Google Scholar]
- Bellanti J. A., Zeligs B. J., Vetro S., Pung Y. H., Luccioli S., Malavasic M. J., Hooke A. M., Ubertini T. R., Vanni R., Nencioni L. Studies of safety, infectivity and immunogenicity of a new temperature-sensitive (ts) 51-1 strain of Salmonella typhi as a new live oral typhoid fever vaccine candidate. Vaccine. 1993;11(5):587–590. doi: 10.1016/0264-410x(93)90238-s. [DOI] [PubMed] [Google Scholar]
- Curtiss R., 3rd, Galan J. E., Nakayama K., Kelly S. M. Stabilization of recombinant avirulent vaccine strains in vivo. Res Microbiol. 1990 Sep-Oct;141(7-8):797–805. doi: 10.1016/0923-2508(90)90113-5. [DOI] [PubMed] [Google Scholar]
- Curtiss R., 3rd, Kelly S. M. Salmonella typhimurium deletion mutants lacking adenylate cyclase and cyclic AMP receptor protein are avirulent and immunogenic. Infect Immun. 1987 Dec;55(12):3035–3043. doi: 10.1128/iai.55.12.3035-3043.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Curtiss R., 3rd, Kelly S. M., Tinge S. A., Tacket C. O., Levine M. M., Srinivasan J., Koopman M. Recombinant Salmonella vectors in vaccine development. Dev Biol Stand. 1994;82:23–33. [PubMed] [Google Scholar]
- Curtiss R., 3rd, Nakayama K., Kelly S. M. Recombinant avirulent Salmonella vaccine strains with stable maintenance and high level expression of cloned genes in vivo. Immunol Invest. 1989 Jan-May;18(1-4):583–596. doi: 10.3109/08820138909112265. [DOI] [PubMed] [Google Scholar]
- Czerkinsky C., Svennerholm A. M., Quiding M., Jonsson R., Holmgren J. Antibody-producing cells in peripheral blood and salivary glands after oral cholera vaccination of humans. Infect Immun. 1991 Mar;59(3):996–1001. doi: 10.1128/iai.59.3.996-1001.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Delos S., Villar M. T., Hu P., Peterson D. L. Cloning, expression, isolation and characterization of the pre-S domains of hepatitis B surface antigen, devoid of the S protein. Biochem J. 1991 Jun 1;276(Pt 2):411–416. doi: 10.1042/bj2760411. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ferreccio C., Levine M. M., Rodriguez H., Contreras R. Comparative efficacy of two, three, or four doses of TY21a live oral typhoid vaccine in enteric-coated capsules: a field trial in an endemic area. J Infect Dis. 1989 Apr;159(4):766–769. doi: 10.1093/infdis/159.4.766. [DOI] [PubMed] [Google Scholar]
- Forrest B. D. Impairment of immunogenicity of Salmonella typhi Ty21a due to preexisting cross-reacting intestinal antibodies. J Infect Dis. 1992 Jul;166(1):210–212. doi: 10.1093/infdis/166.1.210. [DOI] [PubMed] [Google Scholar]
- Forrest B. D. Indirect measurement of intestinal immune responses to an orally administered attenuated bacterial vaccine. Infect Immun. 1992 May;60(5):2023–2029. doi: 10.1128/iai.60.5.2023-2029.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Forrest B. D., LaBrooy J. T., Beyer L., Dearlove C. E., Shearman D. J. The human humoral immune response to Salmonella typhi Ty21a. J Infect Dis. 1991 Feb;163(2):336–345. doi: 10.1093/infdis/163.2.336. [DOI] [PubMed] [Google Scholar]
- Forrest B. D., LaBrooy J. T., Dearlove C. E., Shearman D. J. Effect of parenteral immunization on the intestinal immune response to Salmonella typhi Ty21a. Infect Immun. 1992 Feb;60(2):465–471. doi: 10.1128/iai.60.2.465-471.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Forrest B. D., LaBrooy J. T., Robinson P., Dearlove C. E., Shearman D. J. Specific immune response in the human respiratory tract following oral immunization with live typhoid vaccine. Infect Immun. 1991 Mar;59(3):1206–1209. doi: 10.1128/iai.59.3.1206-1209.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Forrest B. D., Shearman D. J., LaBrooy J. T. Specific immune response in humans following rectal delivery of live typhoid vaccine. Vaccine. 1990 Jun;8(3):209–212. doi: 10.1016/0264-410x(90)90047-p. [DOI] [PubMed] [Google Scholar]
- Galán J. E., Nakayama K., Curtiss R., 3rd Cloning and characterization of the asd gene of Salmonella typhimurium: use in stable maintenance of recombinant plasmids in Salmonella vaccine strains. Gene. 1990 Sep 28;94(1):29–35. doi: 10.1016/0378-1119(90)90464-3. [DOI] [PubMed] [Google Scholar]
- Germanier R., Füer E. Isolation and characterization of Gal E mutant Ty 21a of Salmonella typhi: a candidate strain for a live, oral typhoid vaccine. J Infect Dis. 1975 May;131(5):553–558. doi: 10.1093/infdis/131.5.553. [DOI] [PubMed] [Google Scholar]
- Hahn-Zoric M., Carlsson B., Jalil F., Mellander L., Germanier R., Hanson L. A. The influence on the secretory IgA antibody levels in lactating women of oral typhoid and parenteral cholera vaccines given alone or in combination. Scand J Infect Dis. 1989;21(4):421–426. doi: 10.3109/00365548909167447. [DOI] [PubMed] [Google Scholar]
- Haneberg B., Aarskog D. Human faecal immunoglobulins in healthy infants and children, and in some with diseases affecting the intestinal tract or the immune system. Clin Exp Immunol. 1975 Nov;22(2):210–222. [PMC free article] [PubMed] [Google Scholar]
- Haneberg B., Kendall D., Amerongen H. M., Apter F. M., Kraehenbuhl J. P., Neutra M. R. Induction of specific immunoglobulin A in the small intestine, colon-rectum, and vagina measured by a new method for collection of secretions from local mucosal surfaces. Infect Immun. 1994 Jan;62(1):15–23. doi: 10.1128/iai.62.1.15-23.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hone D. M., Tacket C. O., Harris A. M., Kay B., Losonsky G., Levine M. M. Evaluation in volunteers of a candidate live oral attenuated Salmonella typhi vector vaccine. J Clin Invest. 1992 Aug;90(2):412–420. doi: 10.1172/JCI115876. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hopkins S., Kraehenbuhl J. P., Schödel F., Potts A., Peterson D., de Grandi P., Nardelli-Haefliger D. A recombinant Salmonella typhimurium vaccine induces local immunity by four different routes of immunization. Infect Immun. 1995 Sep;63(9):3279–3286. doi: 10.1128/iai.63.9.3279-3286.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jiang Z. D., Nelson A. C., Mathewson J. J., Ericsson C. D., DuPont H. L. Intestinal secretory immune response to infection with Aeromonas species and Plesiomonas shigelloides among students from the United States in Mexico. J Infect Dis. 1991 Nov;164(5):979–982. doi: 10.1093/infdis/164.5.979. [DOI] [PubMed] [Google Scholar]
- Kantele A., Mäkelä P. H. Different profiles of the human immune response to primary and secondary immunization with an oral Salmonella typhi Ty21a vaccine. Vaccine. 1991 Jun;9(6):423–427. doi: 10.1016/0264-410x(91)90129-t. [DOI] [PubMed] [Google Scholar]
- Kelly S. M., Bosecker B. A., Curtiss R., 3rd Characterization and protective properties of attenuated mutants of Salmonella choleraesuis. Infect Immun. 1992 Nov;60(11):4881–4890. doi: 10.1128/iai.60.11.4881-4890.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Levine M. M., Herrington D., Murphy J. R., Morris J. G., Losonsky G., Tall B., Lindberg A. A., Svenson S., Baqar S., Edwards M. F. Safety, infectivity, immunogenicity, and in vivo stability of two attenuated auxotrophic mutant strains of Salmonella typhi, 541Ty and 543Ty, as live oral vaccines in humans. J Clin Invest. 1987 Mar;79(3):888–902. doi: 10.1172/JCI112899. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McDermott M. R., Bienenstock J. Evidence for a common mucosal immunologic system. I. Migration of B immunoblasts into intestinal, respiratory, and genital tissues. J Immunol. 1979 May;122(5):1892–1898. [PubMed] [Google Scholar]
- Ogra P. L., Ogra S. S. Local antibody response to poliovaccine in the human female genital tract. J Immunol. 1973 May;110(5):1307–1311. [PubMed] [Google Scholar]
- Schödel F., Kelly S. M., Peterson D. L., Milich D. R., Curtiss R., 3rd Hybrid hepatitis B virus core-pre-S proteins synthesized in avirulent Salmonella typhimurium and Salmonella typhi for oral vaccination. Infect Immun. 1994 May;62(5):1669–1676. doi: 10.1128/iai.62.5.1669-1676.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schödel F., Kelly S., Tinge S., Hopkins S., Peterson D., Milich D., Curtiss R., 3rd Hybrid hepatitis B virus core antigen as a vaccine carrier moiety. II. Expression in avirulent Salmonella spp. for mucosal immunization. Adv Exp Med Biol. 1996;397:15–21. [PubMed] [Google Scholar]
- Schödel F., Milich D. R., Will H. Hepatitis B virus nucleocapsid/pre-S2 fusion proteins expressed in attenuated Salmonella for oral vaccination. J Immunol. 1990 Dec 15;145(12):4317–4321. [PubMed] [Google Scholar]
- Schödel F. Prospects for oral vaccination using recombinant bacteria expressing viral epitopes. Adv Virus Res. 1992;41:409–446. doi: 10.1016/s0065-3527(08)60041-x. [DOI] [PubMed] [Google Scholar]
- Silva B. A., Gonzalez C., Mora G. C., Cabello F. Genetic characteristics of the Salmonella typhi strain Ty21a vaccine. J Infect Dis. 1987 May;155(5):1077–1078. doi: 10.1093/infdis/155.5.1077. [DOI] [PubMed] [Google Scholar]
- Srinivasan J., Tinge S., Wright R., Herr J. C., Curtiss R., 3rd Oral immunization with attenuated Salmonella expressing human sperm antigen induces antibodies in serum and the reproductive tract. Biol Reprod. 1995 Aug;53(2):462–471. doi: 10.1095/biolreprod53.2.462. [DOI] [PubMed] [Google Scholar]
- Tacket C. O., Forrest B., Morona R., Attridge S. R., LaBrooy J., Tall B. D., Reymann M., Rowley D., Levine M. M. Safety, immunogenicity, and efficacy against cholera challenge in humans of a typhoid-cholera hybrid vaccine derived from Salmonella typhi Ty21a. Infect Immun. 1990 Jun;58(6):1620–1627. doi: 10.1128/iai.58.6.1620-1627.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tacket C. O., Hone D. M., Curtiss R., 3rd, Kelly S. M., Losonsky G., Guers L., Harris A. M., Edelman R., Levine M. M. Comparison of the safety and immunogenicity of delta aroC delta aroD and delta cya delta crp Salmonella typhi strains in adult volunteers. Infect Immun. 1992 Feb;60(2):536–541. doi: 10.1128/iai.60.2.536-541.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tacket C. O., Hone D. M., Losonsky G. A., Guers L., Edelman R., Levine M. M. Clinical acceptability and immunogenicity of CVD 908 Salmonella typhi vaccine strain. Vaccine. 1992;10(7):443–446. doi: 10.1016/0264-410x(92)90392-w. [DOI] [PubMed] [Google Scholar]
- Vos J. G., Buys J., Hanstede J. G., Hagenaars A. M. Comparison of enzyme-linked immunosorbent assay and passive hemagglutination method for quantification of antibodies to lipopolysaccharide and tetanus toxoid in rats. Infect Immun. 1979 Jun;24(3):798–803. doi: 10.1128/iai.24.3.798-803.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Waldman R. H., Cruz J. M., Rowe D. S. Intravaginal immunization of humans with Candida albicans. J Immunol. 1972 Oct;109(4):662–664. [PubMed] [Google Scholar]
- Wu H. Y., Russell M. W. Induction of mucosal immunity by intranasal application of a streptococcal surface protein antigen with the cholera toxin B subunit. Infect Immun. 1993 Jan;61(1):314–322. doi: 10.1128/iai.61.1.314-322.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]