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Review
doi: 10.1186/1741-7007年8月12日9.

Immunogenicity and efficacy of oral vaccines in developing countries: lessons from a live cholera vaccine

Affiliations
Review

Immunogenicity and efficacy of oral vaccines in developing countries: lessons from a live cholera vaccine

Myron M Levine. BMC Biol. .

Abstract

Oral vaccines, whether living or non-living, viral or bacterial, elicit diminished immune responses or have lower efficacy in developing countries than in developed countries. Here I describe studies with a live oral cholera vaccine that include older children no longer deriving immune support from breast milk or maternal antibodies and that identify some of the factors accounting for the lower immunogenicity, as well as suggesting counter-measures that may enhance the effectiveness of oral immunization in developing countries. The fundamental breakthrough is likely to require reversing effects of the 'environmental enteropathy' that is often present in children living in fecally contaminated, impoverished environments.

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Figures

Figure 1
Figure 1
Cholera-endemic living conditions. (a) Conditions of ramshackle housing, poor sanitation and widespread fecal contamination prevalent in North Jakarta in the early 1990s when phase 2 pediatric clinical trials with CVD 103-HgR live oral cholera vaccine were carried out. (b) Similar conditions of inadequate housing, lack of sanitation and fecally contaminated surface waters in a favella (periurban slum) in São Paulo, Brazil of the type in which environmental enteropathy was first described by Fagundes Neto. Photograph kindly provided by Ulysses Fagundes Neto, Universidade Federal de São Paulo.
Figure 2
Figure 2
Normal intestinal mucosa. Biopsy of the second portion of the duodenum of an 8-year-old US child showing normal histology of the intestinal mucosa. Long, finger-like villi and relatively shallow crypts are evident. The villi are populated with columnar epithelial cells (enterocytes) that have brush borders containing enzymes for digestion and absorption; mucus-producing goblet cells are interspersed among the enterocytes. Less than 20 intraepithelial lymphocytes per 100 enterocytes are present. Photomicrograph kindly provided by Steven Czinn, University of Maryland Medical Center.
Figure 3
Figure 3
Intestinal mucosa showing environmental enteropathy. (a) Biopsy of the distal duodenum of a 36-month old Brazilian child with environmental enteropathy. Moderate villous atrophy is seen with blunted, flat villi and enterocytes that seem somewhat cuboidal rather than columnar. Elongated crypts can be seen, which result in an abnormal crypt to villus ratio. Most prominent is the striking increase in the number of lymphocytes and plasmacytes present in the lamina propria. (b) Biopsy of the distal duodenum of another Brazilian pre-school age child with environmental enteropathy. The changes are as described for (a) but the villous blunting and hypercellularity within the lamina propria are even more prominent. Photomicrographs kindly provided by Ulysses Fagundes Neto, Universidade Federal de São Paulo.

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