Protein Energy Malnutrition during Vaccination Has Limited Influence on Vaccine Efficacy but Abolishes Immunity if Administered during Mycobacterium tuberculosis Infection

Hoang, Truc; Agger, Else Marie; Cassidy, Joseph P.; Christensen, Jan Pravsgaard; Andersen, Peter

doi:10.1128/iai.03030-14

Cited by 26 publications

(22 citation statements)

References 52 publications

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“…Typhi vector, but PM at the time of infection impairs vaccine-boosted immunity and does not protect against Cryptosporidium challenge. Similar effects were seen during PM and a multistage antigen-based Mycobacterium tuberculosis vaccine-challenge model in mice [ 63 ]. Since our investigation began, it has been recognized that an oral route may more optimally target vaccine responses to the small intestine than the intranasal route used in our studies, including Cryptosporidium antigens expressed in an attenuated S .…”

Section: Discussionmentioning

confidence: 58%

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

et al. 2016

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Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children.

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Section: Discussionmentioning

confidence: 58%

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

et al. 2016

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“…T EM produced less IFN-γ upon LCMV peptide restimulation, and had impaired proliferative responses and higher viral loads post-challenge, indicative of functionally impaired immunological memory to LCMV [64] . In a separate study, PEM mice had more Mycobacterium tuberculosis bacilli in their lungs and reduced clearance post-vaccination compared to protein-sufficient mice, which was attributed to reduced lung CD4 + T cell IFN-γ, TNF-α, and IL-2 responses to mycobacterial antigens [73] . It is promising that, in both the LCMV and tuberculosis models, improved diet led to reconstitution of memory T cell responses and improved pathogen clearance in malnourished animals 64 , 73 .…”

Section: Immune Priming and Memory Responsesmentioning

confidence: 95%

“…Current nutritional interventions do not fully reverse morbidity or in undernutrition [8] , but immune function is transiently improved following therapeutic feeding both in humans 11 , 12 , 79 and animals 41 , 64 , 73 . The roles of defined dietary nutrients in immune priming and gut function 38 , 49 support development of therapeutic foods to promote immune recovery in malnutrition (immunonutrition).…”

Section: Targeting Immunopathogenic Pathways In Malnutritionmentioning

confidence: 99%

Immune Dysfunction as a Cause and Consequence of Malnutrition

Bourke

Berkley

Prendergast

2016

Trends in Immunology

515

382

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Malnutrition, which encompasses under- and overnutrition, is responsible for an enormous morbidity and mortality burden globally. Malnutrition results from disordered nutrient assimilation but is also characterized by recurrent infections and chronic inflammation, implying an underlying immune defect. Defects emerge before birth via modifications in the immunoepigenome of malnourished parents, and these may contribute to intergenerational cycles of malnutrition. This review summarizes key recent studies from experimental animals, in vitro models, and human cohorts, and proposes that immune dysfunction is both a cause and a consequence of malnutrition. Focusing on childhood undernutrition, we highlight gaps in current understanding of immune dysfunction in malnutrition, with a view to therapeutically targeting immune pathways as a novel means to reduce morbidity and mortality.

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“…The remarkable differences in efficacy in various trials for TB and leprosy have been ascribed to several factors, including diversity in the genetic fingerprints of the mycobacterial pathogens in different geographic areas ( 35 , 36 ), the various BCG strains used in the studies ( 37 , 38 ), the immune, nutritional, and socioeconomic status of the vaccinees enrolled ( 39 ), the presence of helminths or viral coinfections ( 21 , 40 , 41 ), the background exposure to and induction of immunity by environmental mycobacteria, which might mask or block the effects of BCG ( 42 ), but the precise reasons for this remain largely unclear.…”

Section: Bacille Calmette–guérin (Bcg) One Vaccine Fits All?mentioning

confidence: 99%

Vaccines for Leprosy and Tuberculosis: Opportunities for Shared Research, Development, and Application

et al. 2018

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Tuberculosis (TB) and leprosy still represent significant public health challenges, especially in low- and lower middle-income countries. Both poverty-related mycobacterial diseases require better tools to improve disease control. For leprosy, there has been an increased emphasis on developing tools for improved detection of infection and early diagnosis of disease. For TB, there has been a similar emphasis on such diagnostic tests, while increased research efforts have also focused on the development of new vaccines. Bacille Calmette–Guérin (BCG), the only available TB vaccine, provides insufficient and inconsistent protection to pulmonary TB in adults. The impact of BCG on leprosy, however, is significant, and the introduction of new TB vaccines that might replace BCG could, therefore, have serious impact also on leprosy. Given the similarities in antigenic makeup between the pathogens Mycobacterium tuberculosis (Mtb) and M. leprae, it is well possible, however, that new TB vaccines could cross-protect against leprosy. New TB subunit vaccines currently evaluated in human phase I and II studies indeed often contain antigens with homologs in M. leprae. In this review, we discuss pre-clinical studies and clinical trials of subunit or whole mycobacterial vaccines for TB and leprosy and reflect on the development of vaccines that could provide protection against both diseases. Furthermore, we provide the first preclinical evidence of such cross-protection by Mtb antigen 85B (Ag85B)-early secretory antigenic target (ESAT6) fusion recombinant proteins in in vivo mouse models of Mtb and M. leprae infection. We propose that preclinical integration and harmonization of TB and leprosy research should be considered and included in global strategies with respect to cross-protective vaccine research and development.

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Protein Energy Malnutrition during Vaccination Has Limited Influence on Vaccine Efficacy but Abolishes Immunity if Administered during Mycobacterium tuberculosis Infection

Cited by 26 publications

References 52 publications

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Immune Dysfunction as a Cause and Consequence of Malnutrition

Vaccines for Leprosy and Tuberculosis: Opportunities for Shared Research, Development, and Application

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