Malnutrition and vaccination in developing countries

Prendergast, Andrew J.

doi:10.1098/rstb.2014.0141

Cited by 124 publications

(121 citation statements)

References 73 publications

(118 reference statements)

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“…There have been several hypotheses to explain the variation in immune responses after mucosal vaccination. For example, malnutrition may contribute to oral vaccination in developing countries . In addition, an unsanitary environment in developing countries could lead to persistent exposure of people to various enteric pathogens, which may be associated with reduced efficacy of mucosal vaccines .…”

Section: Discussionmentioning

confidence: 99%

Recognition of the microbiota by Nod2 contributes to the oral adjuvant activity of cholera toxin through the induction of interleukin‐1β

Kim

et al. 2019

Immunology

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The role of symbiotic bacteria in the development of antigen-specific immunity remains poorly understood. Previous studies showed that sensing of symbiotic bacteria by nucleotide-binding oligomerization domaincontaining protein 2 (Nod2) regulates antibody responses in response to nasal immunization with antigen and cholera toxin (CT). In this study, we examined the role of the microbiota in the adjuvant activity of CT induced after oral immunization with antigen. Germ-free (GF) mice showed impaired production of antibody responses and T-cell-specific cytokines after oral immunization when compared with that observed in conventionally raised mice. Similar to GF mice, Nod2-deficient mice showed reduced humoral responses upon oral immunization with antigen and CT. Treatment with CT enhanced the production of interleukin-1b (IL-1b), but not tumor necrosis factor-a or IL-12p40, induced by stimulation of dendritic cells with muramyl dipeptide, the Nod2 ligand. Mechanistically, the enhanced production of IL-1b induced by muramyl dipeptide and CT stimulation required Nod2 and was mediated by both increased synthesis of pro-IL-1b and caspase-1 activation. Furthermore, antigen-specific antibody and cytokine responses induced by CT were impaired in orally immunized IL-1b-deficient mice. Collectively, our results indicate that Nod2 stimulation by symbiotic bacteria contributes to optimal CT-mediated antigen-specific oral vaccination through the induction of IL-1b production.

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Section: Discussionmentioning

confidence: 99%

Recognition of the microbiota by Nod2 contributes to the oral adjuvant activity of cholera toxin through the induction of interleukin‐1β

Kim

et al. 2019

Immunology

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“…The reduced circulating B-cell numbers seen in malnourished children may also impair the host's ability to resolve NTS infection (123). Because reduced B-cell numbers appear not to be accompanied by either reduced antibody levels or altered vaccine responses (124), any effect of reduced B-cell numbers appears likely independent of antibody. Data derived from the mouse model of invasive Salmonella infection suggest an antibodyindependent role for B cells in anti-Salmonella immunity, which is dependent on T H 1 responses (125).…”

Section: Effects Of Malnutrition On Anti-nts Immunitymentioning

confidence: 99%

Invasive Nontyphoidal Salmonella Disease in Africa

Gilchrist

MacLennan²

2019

EcoSal Plus

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Nontyphoidal salmonellae (NTS) are a major cause of invasive (iNTS) disease in sub-Saharan Africa, manifesting as bacteremia and meningitis. Available epidemiological data indicate that iNTS disease is endemic in much of the region. Antimicrobial resistance is common and case fatality rates are high. There are well-characterized clinical associations with iNTS disease, including young age, HIV infection, malaria, malnutrition, anemia, and sickle cell disease. However, the clinical presentation of iNTS disease is often with fever alone, so clinical diagnosis is impossible without blood culture confirmation. No vaccine is currently available, making this a priority area for global health research. Over the past ten years, it has emerged that iNTS disease in Africa is caused by distinct pathovars of Salmonella Typhimurium, belonging to sequence type ST313, and Salmonella Enteritidis. These are characterized by genome degradation and appear to be adapting to an invasive lifestyle. Investigation of rare patients with primary immunodeficiencies has suggested a key role for interferon gamma–mediated immunity in host defense against NTS. This concept has been supported by recent population-based host genetic studies in African children. In contrast, immunoepidemiological studies from Africa indicate an important role for antibody for protective immunity, supporting the development of antibody-inducing vaccines against iNTS disease. With candidate O-antigen–based vaccines due to enter clinical trials in the near future, research efforts should focus on understanding the relative contributions of antibody and cell-mediated immunity to protection against iNTS disease in humans.

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“…Several abnormalities in immune function have been linked with malnutrition, including deficits in secretory IgA, complement production, gut barrier function and T-cell memory maintenance, among others [107]. In spite of these immunological deficits, a consistent link between malnutrition and oral vaccine performance has not been found [108,109]. A recent study among infants in Bangladesh documented significantly lower serotype 3 poliovirus antibody titers in conjunction with underweight (weight-for-age Z score ≤2) after at least three doses of OPV [65].…”

Section: Malnutrition and Micronutrient Deficienciesmentioning

confidence: 99%

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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Malnutrition and vaccination in developing countries

Cited by 124 publications

References 73 publications

Recognition of the microbiota by Nod2 contributes to the oral adjuvant activity of cholera toxin through the induction of interleukin‐1β

Recognition of the microbiota by Nod2 contributes to the oral adjuvant activity of cholera toxin through the induction of interleukin‐1β

Invasive Nontyphoidal Salmonella Disease in Africa

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

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