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. 2014 Jan 15;9(1):e83999.
doi: 10.1371/journal.pone.0083999. eCollection 2014.

Age-dependent association among Helicobacter pylori infection, serum pepsinogen levels and immune response of children to live oral cholera vaccine CVD 103-HgR

Khitam Muhsen  1 , Rosanna Lagos  2 , Mardi K Reymann  1 , David Y Graham  3 , Marcela F Pasetti  4 , Myron M Levine  1
Affiliations

Age-dependent association among Helicobacter pylori infection, serum pepsinogen levels and immune response of children to live oral cholera vaccine CVD 103-HgR

Khitam Muhsen et al. PLoS One. .

Abstract

Background: Through its effects on gastric secretion, we hypothesized that Helicobacter pylori infection may influence oral immunization. Accordingly, we examined the association between H. pylori infection, serum pepsinogen (PG) (measures for H. pylori gastritis) and vibriocidal antibody (a correlate of protection) seroconversion following oral immunization with CVD 103-HgR live cholera vaccine among children of different ages.

Methods: Sera from 422 Chilean children who were vaccinated with a single dose of CVD 103-HgR were tested by ELISA for serum IgG antibodies to H. pylori, PG I and PG II levels and antibodies to Shigella flexneri 2a lipopolysaccharide and hepatitis A virus (as markers of low socioeconomic status and exposure to enteric pathogens).

Results: The likelihood of vibriocidal antibody seroconversion following vaccination with CVD 103-HgR was significantly decreased in H. pylori-seropositive children age 6 months to 4 years with PG II>8 µg/L (adjusted OR 0.14 (95% CI 0.03-0.61; P = 0.009), and also in H. pylori seropositives with lower PG II level (adjusted OR 0.34, 95% CI 0.14-0.83; P = 0.017), compared to H. pylori-seronegatives. H. pylori-seropositive children aged 5-9 years with serum PG I>30 µg/L (indicating more severe gastritis) had higher odds of vibriocidal seroconversion than those with lower PG I levels (adjusted OR 4.41, 95%CI 1.26-15.38; P = 0.02). There was no significant association between exposures to S. flexneri 2a or hepatitis A virus and vibriocidal seroconversion.

Conclusions: As H. pylori gastritis progresses with increasing pediatric age in developing country venues, changes in gastric secretion ensue that we believe explain the observed differences in age-related immune responses to immunization with live oral cholera vaccine. The effect of H. pylori and changes of gastric acid secretion on the immunogenicity of various oral vaccines should be studied in different developing, transitional and industrialized country settings.

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Conflict of interest statement

Competing Interests: The authors have the following interests. Professor M.M. Levine is co-inventor of the CVD 103-HgR oral cholera vaccine and co-holder of related patents. At present CVD 103-HgR is not available commercially. However, PaxVax, a vaccine manufacturer in San Diego, CA, USA, has initiated a clinical development program to re-commercialize CVD 103-HgR (as VibrioVax®) and return it to market as a licensed vaccine within the next few years. There are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. Patents related to live oral cholera vaccine CVD 103-HgR: Kaper, James B. and Levine, Myron M. U.S. patent # 5,628,994, “Vibrio cholerae strain CVD 103-HgR, method of making same and vaccines derived therefrom”. Patent was issued on May 13, 1997.

Figures

Figure 1
Figure 1. The Prevalence (%) of Helicobacter pylori infection by age.
See this image and copyright information in PMC

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