Administration of purified colonization factor antigens (CFA/I, CFA/II) of enterotoxigenic Escherichia coli to volunteers. Response to challenge with virulent enterotoxigenic Escherichia coli

Gastroenterology. 1984 Oct;87(4):934-40.

Abstract

Colonization factor antigens (CFAs) were administered orally to volunteers, and the mucosal immune response was assessed by measuring secretory immunoglobulin A (IgA) in saliva and intestinal secretions and by challenge with virulent enterotoxigenic Escherichia coli (ETEC). A combination of CFA/I and CFA/II (8 mg each) administered orally in four doses in milk failed to induce a mucosal IgA response and also failed to protect against challenge with CFA-positive ETEC. When CFA was administered orally (1.5 mg divided into three doses with bicarbonate) to volunteers without preexisting serum anti-CFA levels, it failed to elicit a serum IgG or intestinal secretory IgA response or to protect against challenge with virulent ETEC. The CFA is destroyed by acid gastric contents but it induced significant antibody titer rises in 8 of 11 (73%) volunteers with preexisting serum anti-CFA IgG levels after oral administration of 1 mg of CFA/I with sodium bicarbonate. Subcutaneous priming (50 micrograms CFA/I) did not induce a serum IgG response but, when followed by oral boosting (1 mg CFA/I in two divided doses with sodium bicarbonate), induced intestinal anti-CFA secretory IgA in 4 of 8 volunteers and protected against challenge with CFA/I-positive ETEC. These results, although preliminary, are encouraging and demonstrate that it may be possible to develop an effective oral vaccine based on soluble nonreplicating antigens such as purified CFAs.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Antibodies, Bacterial / biosynthesis
  • Antigens, Bacterial / administration & dosage*
  • Bacterial Vaccines / administration & dosage*
  • Diarrhea / etiology
  • Diarrhea / prevention & control*
  • Escherichia coli / immunology*
  • Escherichia coli / pathogenicity
  • Escherichia coli Infections / complications
  • Escherichia coli Infections / prevention & control*
  • Feces / microbiology
  • Female
  • Fimbriae Proteins*
  • Humans
  • Immunoglobulin A / biosynthesis
  • Immunoglobulin G / biosynthesis
  • Injections, Subcutaneous
  • Male
  • Virulence

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Vaccines
  • Immunoglobulin A
  • Immunoglobulin G
  • colonization factor antigens
  • Fimbriae Proteins