We propose a collaborative research program to carry out field studies of bacterial enteric vaccine candidates in Santiago, Chile in conjunction with the Servicio de Salud Metropolitano Norte, the Universidad de Chile, Roberto del Rio Children's Hospital and the Ministry of Health. The studies will attempt to optimize oral immunization so that young children can be successfully immunized with a single dose of vaccine. Projected studies would investigate the clinical acceptability and immunogenicity of single-dose live oral recombinant cholera vaccine strain CVD 103-HgR in toddlers and infants. If a single dose of this oral vaccine is indeed well-tolerated and immunogenic in young infants, this would provide support for the concept of the Children's Vaccine Initiative. A number of oral vaccines (e.g., attenuated poliovirus vaccine) exhibit diminished immunogenicity in low socioeconomic level children in less-developed countries. Using CVD 103-HgR as a model, we will investigate the hypothesis that such diminished immunogenicity is in part due to small bowel bacterial overgrowth (environmental enteropathy). We will perform non-invasive breath H2 tests in Santiago schoolchildren to screen for small bowel bacterial overgrowth, prior to administering a dose of CVD 103-HgR vaccine to the children. The magnitude of the vibriocidal antibody response will be compared in children with and without small bowel overgrowth. Studies will be carried out in young children to establish the safety and immunogenicity of multivalent vaccines against Shigella and enterotoxigenic Escherichia coli (ETEC), important pathogens of diarrhea disease among children in developing countries. The ETEC vaccine will be a live vector vaccine in which ETEC colonization factor fimbriae and B subunit of heat-labile enterotoxin are expressed in attenuated live vectors. By maintaining prospective surveillance at two health centers that serve large populations of low socioeconomic level, we shall prepare a field site in which we propose to carry out a large-scale field trial of efficacy of a multivalent vaccine against Shigella or ETEC. The groups of U.S. and Chilean investigators and their institutions have a long history of productive and harmonious collaboration.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI035948-04
Application #
2429422
Study Section
Special Emphasis Panel (SRC (37))
Project Start
1994-09-01
Project End
1999-05-31
Budget Start
1997-06-01
Budget End
1998-05-31
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Muhsen, Khitam; Lagos, Rosanna; Reymann, Mardi K et al. (2014) Age-dependent association among Helicobacter pylori infection, serum pepsinogen levels and immune response of children to live oral cholera vaccine CVD 103-HgR. PLoS One 9:e83999
Lagos, Rosanna; Munoz, Alma; Valenzuela, Maria Teresa et al. (2002) Population-based surveillance for hospitalized and ambulatory pediatric invasive pneumococcal disease in Santiago, Chile. Pediatr Infect Dis J 21:1115-23
Richie, E E; Punjabi, N H; Sidharta, Y Y et al. (2000) Efficacy trial of single-dose live oral cholera vaccine CVD 103-HgR in North Jakarta, Indonesia, a cholera-endemic area. Vaccine 18:2399-410
Lagos, R; Avendano, L F; Levine, M M (1999) [Systematic surveillance of influenza, syncytial respiratory, parainfluenza and adenovirus in children with acute respiratory infections] Rev Med Chil 127:1063-72
Levine, O S; Lagos, R; Munoz, A et al. (1999) Defining the burden of pneumonia in children preventable by vaccination against Haemophilus influenzae type b. Pediatr Infect Dis J 18:1060-4
Levine, M M; Ferreccio, C; Abrego, P et al. (1999) Duration of efficacy of Ty21a, attenuated Salmonella typhi live oral vaccine. Vaccine 17 Suppl 2:S22-7
Lagos, R; Fasano, A; Wasserman, S S et al. (1999) Effect of small bowel bacterial overgrowth on the immunogenicity of single-dose live oral cholera vaccine CVD 103-HgR. J Infect Dis 180:1709-12
Prado, V; Lagos, R; Nataro, J P et al. (1999) Population-based study of the incidence of Shigella diarrhea and causative serotypes in Santiago, Chile. Pediatr Infect Dis J 18:500-5
Lagos, R; San Martin, O; Wasserman, S S et al. (1999) Palatability, reactogenicity and immunogenicity of engineered live oral cholera vaccine CVD 103-HgR in Chilean infants and toddlers. Pediatr Infect Dis J 18:624-30
Lagos, R; Levine, O S; Avendano, A et al. (1998) The introduction of routine Haemophilus influenzae type b conjugate vaccine in Chile: a framework for evaluating new vaccines in newly industrializing countries. Pediatr Infect Dis J 17:S139-48

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