Supplementation with Zinc, but Not Vitamin A, Improves Seroconversion to Vibriocidal Antibody in Children Given an Oral Cholera Vaccine

Albert, M. John; Qadri, Firdausi; Wahed, M. A.; Ahmed, Tanvir; Rahman, Ahmed Shafiqur; Ahmed, Firoz; Bhuiyan, N. A.; Zaman, Khalequ; Baqui, Abdullah H; Clemens, John D.; Black, Robert E.

doi:10.1086/368132

Cited by 114 publications

(55 citation statements)

References 14 publications

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“…A potential shortcoming of our study is that our group and others have demonstrated the effect of zinc supplementation (1,3,28), small bowel bacterial overgrowth (20), and antiparasitic drug treatment (8) on immune responses to OCV in young children. We did not assess differences between age groups of such modifiers of immune responses in this study, and these factors deserve further investigation.…”

Section: Discussionmentioning

confidence: 99%

Memory B Cell and Other Immune Responses in Children Receiving Two Doses of an Oral Killed Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh

Leung¹,

Rahman²,

Mohasin³

et al. 2012

Clin. Vaccine Immunol.

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ABSTRACTCurrent oral cholera vaccines induce lower protective efficacy and shorter duration of protection against cholera than wild-type infection provides, and this difference is most pronounced in young children. Despite this, there are limited data comparing immune responses in children following wild-type disease versus vaccination, especially with regard to memory responses associated with long-term immunity. Here, we report a comparison of immune responses in young children (2 to 5 years of age;n= 20) and older children (6 to 17 years of age;n= 20) given two doses of an oral killed cholera vaccine containing recombinant cholera toxin B subunit (CtxB) 14 days apart and compare these responses to those induced in similarly aged children recovering from infection withVibrio choleraeO1 Ogawa in Bangladesh. We found that the two vaccine groups had comparable vibriocidal and lipopolysaccharide (LPS)-specific plasma antibody responses. Vaccinees developed lower levels of IgG memory B cell (MBC) responses against CtxB but no significant MBC responses against LPS. In contrast, children recovering from natural cholera infection developed prominent LPS IgG and IgA MBC responses, as well as CtxB IgG MBC responses. Plasma LPS IgG, IgA, and IgM responses, as well as vibriocidal responses, were also significantly higher in children following disease than after vaccination. Our findings suggest that acute and memory immune responses following oral cholera vaccination in children are significantly lower than those observed following wild-type disease, especially responses targeting LPS. These findings may explain, in part, the lower efficacy of oral cholera vaccination in children.

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Section: Discussionmentioning

confidence: 99%

Memory B Cell and Other Immune Responses in Children Receiving Two Doses of an Oral Killed Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh

Leung¹,

Rahman²,

Mohasin³

et al. 2012

Clin. Vaccine Immunol.

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“…During a trial of CVD 103-HgR in Bangladesh, supplementation with zinc (but not vitamin A) significantly boosted vibriocidal antibody response [118]. Low levels of serum zinc have also been associated with rotavirus risk in Bangladesh [119], though supplementation with zinc did not improve Rotarix immunogenicity during a study in India [120].…”

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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“…It has been estimated that in Bangladesh over 40% of children younger than 5 years of age may have zinc deficiency (131,168). Supplementation with zinc increases the adaptive immune responses to cholera vaccination in children and adults (9,91,131) and in children with shigellosis (140). The effect of micronutrient deficiency on the morbidity and protective immune responses in ETEC diarrhea has not been specifically studied but is an area that needs attention.…”

Section: Etec Infections and Malnutritionmentioning

confidence: 99%

Enterotoxigenic Escherichia coli in Developing Countries: Epidemiology, Microbiology, Clinical Features, Treatment, and Prevention

et al. 2005

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ETEC is an underrecognized but extremely important cause of diarrhea in the developing world where there is inadequate clean water and poor sanitation. It is the most frequent bacterial cause of diarrhea in children and adults living in these areas and also the most common cause of traveler's diarrhea. ETEC diarrhea is most frequently seen in children, suggesting that a protective immune response occurs with age. The pathogenesis of ETEC-induced diarrhea is similar to that of cholera and includes the production of enterotoxins and colonization factors. The clinical symptoms of ETEC infection can range from mild diarrhea to a severe cholera-like syndrome. The effective treatment of ETEC diarrhea by rehydration is similar to treatment for cholera, but antibiotics are not used routinely for treatment except in traveler's diarrhea. The frequency and characterization of ETEC on a worldwide scale are inadequate because of the difficulty in recognizing the organisms; no simple diagnostic tests are presently available. Protection strategies, as for other enteric infections, include improvements in hygiene and development of effective vaccines. Increases in antimicrobial resistance will dictate the drugs used for the treatment of traveler's diarrhea. Efforts need to be made to improve our understanding of the worldwide importance of ETEC

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Supplementation with Zinc, but Not Vitamin A, Improves Seroconversion to Vibriocidal Antibody in Children Given an Oral Cholera Vaccine

Cited by 114 publications

References 14 publications

Memory B Cell and Other Immune Responses in Children Receiving Two Doses of an Oral Killed Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh

Memory B Cell and Other Immune Responses in Children Receiving Two Doses of an Oral Killed Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

Enterotoxigenic Escherichia coli in Developing Countries: Epidemiology, Microbiology, Clinical Features, Treatment, and Prevention

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