Effect of Small Bowel Bacterial Overgrowth on the Immunogenicity of Single‐Dose Live Oral Cholera Vaccine CVD 103‐HgR

Lagos, Rosanna; Fasano, Alessio; Wasserman, Steven S.; Prado, Valeria; Martin, Oriana San; Abrego, Paulina; Losonsky, Genevieve A.; Alegría, S; Levine, Myron M.

doi:10.1086/315051

Cited by 104 publications

(83 citation statements)

References 17 publications

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“…This finding may be of particular relevance in developing countries, where the efficacy of oral vaccines against polio, rotavirus, and cholera have showed a lower immunogenicity relative to efficacy in developed countries (75)(76)(77)(78). In a study testing a live cholera oral vaccine, Lagos et al (79) demonstrated that excessive bacterial growth in the small intestine of children in less-developed countries might contribute to the low antibody response to the vaccine. Therefore, future systems vaccinology studies should integrate metagenomics approaches to determine the composition of microflora that correlates with a particular profile of vaccine immunity.…”

Section: Vaccines For Which There Are No Knownmentioning

confidence: 97%

Systems vaccinology: Probing humanity’s diverse immune systems with vaccines

Pulendran

2014

Proc. Natl. Acad. Sci. U.S.A.

177

123

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Homo sapiens are genetically diverse, but dramatic demographic and socioeconomic changes during the past century have created further diversification with respect to age, nutritional status, and the incidence of associated chronic inflammatory disorders and chronic infections. These shifting demographics pose new challenges for vaccination, as emerging evidence suggests that age, the metabolic state, and chronic infections can exert major influences on the immune system. Thus, a key public health challenge is learning how to reprogram suboptimal immune systems to induce effective vaccine immunity. Recent advances have applied systems biological analysis to define molecular signatures induced early after vaccination that correlate with and predict the later adaptive immune responses in humans. Such "systems vaccinology" approaches offer an integrated picture of the molecular networks driving vaccine immunity, and are beginning to yield novel insights about the immune system. Here we discuss the promise of systems vaccinology in probing humanity's diverse immune systems, and in delineating the impact of genes, the environment, and the microbiome on protective immunity induced by vaccination. Such insights will be critical in reengineering suboptimal immune systems in immunocompromised populations.

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Section: Vaccines For Which There Are No Knownmentioning

confidence: 97%

Systems vaccinology: Probing humanity’s diverse immune systems with vaccines

Pulendran

2014

Proc. Natl. Acad. Sci. U.S.A.

177

123

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“…Owing to the invasive nature of intestinal biopsies, studies of EED have tended to rely on serum and fecal biomarkers, such as those indicative of small bowel bacterial overgrowth (e.g., hydrogen breath test), gut inflammation (e.g., fecal calprotectin and myeloperoxidase), microbial translocation (e.g., serum EndoCab) and mucosal permeability (e.g., lactulose/mannitol test). To date, the study of these biomarkers has failed to yield any consistent associations between EED and oral vaccine performance [28,98,[170][171][172][173], as discussed in detail elsewhere [Church et al, In Preparation].…”

Section: Environmental Enteric Dysfunctionmentioning

confidence: 99%

“…[65], [98], [108], [135], [171], [196] [67], [133][134][135], [198][199][200][201] [8], [181], [182], [201], [203], [204] [28], [92], [93], [128], [131], [137], [138], [140], [130], [131], [157], [202] [ [43][44][45], [49], [61][62][63][64][65][66][67][68][69][70], [197] [ [155][156][157] [28], [98], [170][171][172]…”

Section: Conclusion and Future Perspectiveunclassified

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

et al. 2017

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Oral vaccines are less immunogenic when given to infants in low-income compared with high-income countries, limiting their potential public health impact. Here, we review factors that might contribute to this phenomenon, including transplacental antibodies, breastfeeding, histo blood group antigens, enteric pathogens, malnutrition, microbiota dysbiosis and environmental enteropathy. We highlight several clear risk factors for vaccine failure, such as the inhibitory effect of enteroviruses on oral poliovirus vaccine. We also highlight the ambiguous and at times contradictory nature of the available evidence, which undoubtedly reflects the complex and interconnected nature of the factors involved. Mechanisms responsible for diminished immunogenicity may be specific to each oral vaccine. Interventions aiming to improve vaccine performance may need to reflect the diversity of these mechanisms. Enteric pathogens are a substantial threat to public health. This threat takes many forms, from the toxin-producing bacteria (e.g., Vibrio cholerae) and flagellated protozoa (e.g., Giardia lamblia) that colonize the mucosal surface of the small intestine to the enteroviruses that are capable of spreading via the bloodstream to the CNS, causing acute flaccid paralysis (e.g., poliovirus). Each year, enteric pathogens cause hundreds of millions of cases of diarrhea and approximately 800,000 deaths, the vast majority of which occur among children in low-income countries [1]. The most common causes of childhood diarrheal morbidity include rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli and Shigella [2].Vaccines against enteric pathogens are important tools for mitigating this disease burden. Oral vaccines offer several distinct benefits compared with parenteral vaccines. They can be produced in large quantities at relatively low cost, are easy to administer and have the capacity to induce local immunity in the intestinal mucosa, thereby protecting vaccinated individuals against subsequent infection and -by blocking onward transmission -enhancing herd immunity [3,4]. Currently licensed oral vaccines include live-attenuated poliovirus vaccines containing one, two or three serotypes, live-attenuated rotavirus vaccines (Rotarix R , RotaTeq R , Lanzhou lamb rotavirus vaccine [China only] and Rotavac R [India only]), live-attenuated cholera vaccine (CVD 103-HgR or Vaxchora TM ), inactivated cholera vaccines (Dukoral R and Shanchol R ) and live-attenuated typhoid vaccine (Ty21a). Other oral vaccines are in development, including those against Shigella, enterotoxigenic E. coli, Campylobacter and Clostridium difficile, as well as several novel rotavirus vaccine candidates (including the human neonatal vaccine RV3-BB [5] and an oral bovine pentavalent vaccine [6]).Yet oral vaccines have an Achilles' heel -their immunogenicity and efficacy is impaired in low-income countries that experience the greatest burden of enteric disease (Box 1). For example, Rotarix has a 1-year protective efficacy against severe rotavirus-associated gas...

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“…A recent e¤cacy study in Indonesia generated disappointing protection against cholera. This may, in part, be due to the di¡erent intestinal environment in many individuals in developing compared to developed countries (Lagos et al 1999). The normal £ora and even gut architecture can di¡er enormously between the two groups, and higher doses of CVD103 vaccine were required in locals from the tropics (Thailand) to elicit similar levels of immunity to Westerner (in this case from the USA) (Tacket et al 1992(Tacket et al , 1999Su-Arehawaratana et al 1992).…”

Section: The Immunogenicity Of Live Mucosal Vaccinesmentioning

confidence: 99%

THE IMMUNE RESPONSES TO BACTERIAL ANTIGENS ENCOUNTERED IN VIVO AT MUCOSAL SURFACES

Dougan

Ghaem-Maghami

Pickard

et al. 2001

The Activities of Bacterial Pathogens in Vivo

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Mammals have evolved a sophisticated immune system for handling antigens encountered at their mucosal surfaces. The way in which mucosally delivered antigens are handled in£uences our ability to design e¡ective mucosal vaccines. Live attenuated derivatives of pathogens are one route towards the development of mucosal vaccines. However, some molecules, described as mucosal immunogens, are inherently immunogenic at mucosal surfaces. Studies on mucosal immunogens may facilitate the identi¢-cation of common characteristics that contribute to mucosal immunogenicity and aid the development of novel, non-living mucosal vaccines and immunostimulators.

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Effect of Small Bowel Bacterial Overgrowth on the Immunogenicity of Single‐Dose Live Oral Cholera Vaccine CVD 103‐HgR

Cited by 104 publications

References 17 publications

Systems vaccinology: Probing humanity’s diverse immune systems with vaccines

Systems vaccinology: Probing humanity’s diverse immune systems with vaccines

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

THE IMMUNE RESPONSES TO BACTERIAL ANTIGENS ENCOUNTERED IN VIVO AT MUCOSAL SURFACES

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