Antibody responses and infertility in mice following oral immunization with attenuated Salmonella typhimurium expressing recombinant murine ZP3

Xin Zhang, Ya Huan Lou, Marcel Koopman, Teresa Doggett, Kenneth S K Tung, Roy Curtiss

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Ovarian ZP3, the primary sperm receptor, is a major glycoprotein of mouse zona pellucida (ZP). Because antibodies raised against ZP3 block sperm-egg interaction, ZP3 has been considered a candidate immunogen in the development of a contraceptive vaccine. This study explored the possibility of using an attenuated Salmonella typhimurium vaccine strain expressing recombinant ZP3 to elicit an antibody response and infertility in mice. A cDNA sequence generated by the polymerase chain reaction encoding 342 amino acid residues (23-364) of the mouse (m)ZP3 was cloned into an Asd+ vector. An avirulent Salmonella vaccine strain stably expressed the ZP3 polypeptide and colonized the internal organs of mice after oral inoculation. Oral immunization of female BALB/c mice with the recombinant Salmonella vaccine strain expressing mZP3 induced significant levels of anti-native ZP IgG antibodies in serum and IgA antibodies in vaginal secretions. The IgG antibodies thus induced also bound to ZP in vivo. When mated with males, 3 of 6 females immunized with the recombinant Salmonella were infertile. In contrast, none of the mice that received Salmonella containing the vector plasmid produced antibodies to ZP and all were fertile. No ovarian inflammation was observed in the immunized mice at autopsy. The results suggest a potential oral contraceptive vaccine to control populations of rodent vectors of disease and to induce reversible infertility in humans.

Original languageEnglish (US)
Pages (from-to)33-41
Number of pages9
JournalBiology of Reproduction
Volume56
Issue number1
DOIs
StatePublished - Jan 1997
Externally publishedYes

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Salmonella typhimurium
Infertility
Antibody Formation
Immunization
Salmonella Vaccines
Zona Pellucida
Contraceptive Vaccines
Antibodies
Salmonella
Rodent Diseases
Immunoglobulin G
Sperm-Ovum Interactions
Attenuated Vaccines
Synthetic Vaccines
Oral Contraceptives
Immunoglobulin A
Autopsy
Plasmids
Complementary DNA
Inflammation

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Embryology

Cite this

Antibody responses and infertility in mice following oral immunization with attenuated Salmonella typhimurium expressing recombinant murine ZP3. / Zhang, Xin; Lou, Ya Huan; Koopman, Marcel; Doggett, Teresa; Tung, Kenneth S K; Curtiss, Roy.

In: Biology of Reproduction, Vol. 56, No. 1, 01.1997, p. 33-41.

Research output: Contribution to journalArticle

Zhang, Xin ; Lou, Ya Huan ; Koopman, Marcel ; Doggett, Teresa ; Tung, Kenneth S K ; Curtiss, Roy. / Antibody responses and infertility in mice following oral immunization with attenuated Salmonella typhimurium expressing recombinant murine ZP3. In: Biology of Reproduction. 1997 ; Vol. 56, No. 1. pp. 33-41.
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