1,25‐Dihydroxyvitamin D3 Enhances Systemic and Mucosal Immune Responses to Inactivated Poliovirus Vaccine in Mice

Ivanov, Alexander P.; Dragunsky, Eugenia; Chumakov, Konstantin

doi:10.1086/499970

Cited by 61 publications

(45 citation statements)

References 9 publications

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“…In contrast, the data indicate that induction of TT-specific IgG was marginally more efficient in vitamin D compared with the placebo group (P ¼ 0.04). These data are in line with previous studies (Ivanov et al, 2006;Enioutina et al, 1999Enioutina et al, , 2008Van der Stede et al, 2001) and attributed most likely to induction of specific IgG1, which is the dominant subclass induced by the vaccination used herein (492% of the circulating specific plasmablasts; Frolich et al, 2010). That vitamin D supplementation did not alter the specific Peripheral blood mononuclear cells were activated before and 7 days after a Tet immunization for 24 h in the presence of Tet or SEB, and the secreted cytokines were determined from the supernatants.…”

Section: Discussionsupporting

confidence: 90%

Efficient tetanus toxoid immunization on vitamin D supplementation

et al. 2011

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Background/Objectives: Vitamin D mediates immunomodulatory functions, and its deficiency has been associated with an increased prevalence of immunological diseases. The supplementation of vitamin D might be therapeutically beneficial, for example, in lupus erythematosus patients. However, its affect on established recall immune responses is undefined. Subjects/Methods: In all, 32 individuals were randomized in a placebo controlled, double-blind setting, and received vitamin D (daily 2000 IU) for 10 weeks followed by tetanus toxoid (TT) booster immunization. Results: During vitamin D supplementation the median 25-hydroxyvitamin D serum concentration increased to 80.3 nM, which as expected decreased in the placebo group to 29.1 nM during the ultraviolet-deprived winter months. The TT-specific immunoglobulin G (IgG) boost efficiency was marginal higher in the vitamin D group (P ¼ 0.04). The increase of the 25-hydroxyvitamin D levels correlated with the increase of TT-IgG serum concentrations. The induction of specific serum IgA and specific antibody secreting cells was comparable between both groups. Accordingly, the TT-specific and polyclonally triggered T-cell cytokine profiles were stable as well. Conclusions: Vitamin D supplementation was successful and booster immunization induced efficiently specific antibodies titers.

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Section: Discussionsupporting

confidence: 90%

Efficient tetanus toxoid immunization on vitamin D supplementation

et al. 2011

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“…While the role of vaccinations in the etiology of autism is not clear, higher levels of calcidiol could reduce the risk of adverse reactions to vaccinations, based on reports that calcidiol reduces the risk of respiratory viral infections and that calcitriol enhances the effectiveness of vaccinations. [55][56][57][58] …”

Section: Discussionmentioning

confidence: 99%

Epidemiologic evidence for supporting the role of maternal vitamin D deficiency as a risk factor for the development of infantile autism

Grant

Soles²

2009

Dermato-Endocrinology

130

102

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This study examines whether maternal vitamin D deficiency is a risk factor for infantile autism disease (IAD). We used epidemiologic data seasonal variation of birth rates and prevalence of IAD for cohorts born before 1985. For seven studies reporting spring-to-summer excess birth rates for IAD, the season progressed from broad near 30° N latitude, spring/summer in midlatitudes, to winter at the highest latitude. Also, using data from 10 studies, we found a strong effective latitudinal (related to wintertime solar ultraviolet B radiation) increase in IAD prevalence. These findings are consistent with maternal vitamin D deficiency's being a risk factor for IAD, possibly by affecting fetal brain development as well as possibly by affecting maternal immune system status during pregnancy. Further investigation of this hypothesis is warranted. IntroductionThe etiology of autism is still somewhat of an enigma. Autism is considered an autoimmune disease. 1 It also appears to have important risk factors in utero, as evidenced by a highly significant increased frequency of congenital malformations; 2 and those with autism have several characteristics associated with schizophrenia, 3 which is also linked to in utero risk factors. 4 Perinatal viral infection of mother or infant is a risk factor for both infantile autism and schizophrenia. 5 Also, several studies have reported seasonality in excess births of those with autism, with March being a peak month in Sweden, 6 Denmark 7 and Boston, 8 but without a good explanation for this seasonality.Schizophrenia is another disease that exhibits excess of births in winter and a deficit in summer. 9 This seasonality has sometimes been shown to be linked to influenza epidemics. 10,11 Infectious disease during pregnancy has been found to adversely affect rodent brain development in a manner that can lead to schizophrenia as well as autism. [12][13][14][15][16][17][18] The hypothesis that the seasonality was related to low levels of maternal serum 25-hydroxyvitamin D (calcidiol) was also advanced. 19 Support for the maternal vitamin D deficiency hypothesis has been reported based on rat studies. [20][21][22] It was recently proposed that the annual solar ultraviolet-B (UVB) and vitamin D cycles explained some of the seasonality of epidemic influenza, which peaks in winter. 23 This hypothesis received experimental support in a randomized, prospective, placebo-controlled vitamin D study involving 204 postmenopausal black women living in the state of New York. Those taking 2,000 IU of vitamin D3 per day got 10% as many colds or influenza as those taking the placebo. 24 More support came from a study of meteorological variables associated with incidence of respiratory syncytial virus that found an effect for solar UVB in addition to temperature and relative humidity, with greatest effect at lower latitude. 25 Thus, serum calcidiol levels can affect risk of maternal viral disease during pregnancy.This report examines the evidence supporting the hypothesis that maternal vitamin D deficien...

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“…We and others have previously reported that both systemic and mucosal antigen-specific immune responses can be induced in mice and other animal species following parenteral immunization with protein vaccines containing small quantities of 1α25(OH) 2 D 3 [17][18][19]21,22,37,38]. The mucosal antibody responses induced by these systemically administered vaccines were established to reflect local production by IgA-secreting B cells residing in the lamina propria, and the levels of antigen-specific IgA antibodies present in the mucosal secretions were determined to be independent of serum antibody titers [18].…”

Section: Discussionmentioning

confidence: 99%

TLR ligands that stimulate the metabolism of vitamin D3 in activated murine dendritic cells can function as effective mucosal adjuvants to subcutaneously administered vaccines

Enioutina

Bareyan

Daynes

2008

Vaccine

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Cathelicidin production by human myeloid cells stimulated through toll like receptor (TLR) 2/1, the migration of human CD8 + T cells to inflamed skin sites, and the ability of murine dendritic cells (DCs) to migrate from skin sites of vaccination to mucosal lymphoid organs all occur via calcitrioldependent mechanisms. Herein, we report that murine DCs exposed to TLR3/TLR4 ligands upregulate their expression of 1α-hydroxylase, the enzyme that converts circulating 25(OH)D 3 to calcitriol, the active form of vitamin D3. TLR3/TLR4 ligands injected subcutaneously affect DC migration in vivo, allowing their trafficking to both draining and non-draining systemic and mucosal lymphoid organs. Subcutaneously delivered vaccines containing TLR3/TLR4 ligands and antigen stimulate the induction of both systemic and mucosal immune responses. Vaccines containing TLR9 ligands fail to stimulate 1α-hydroxylase protein expression, are incapable of redirecting DC migration into Peyer's patches and do not induce mucosal immune responses. These findings support a hypothesis that active metabolites of vitamin D3 produced locally are able to affect various aspects of innate and acquired immune responses. Keywords dendritic cells; TLR ligands; mucosal immune response; calcitriol IntroductionIn mammals there are at least 12 members of the toll like receptor (TLR) family. These receptors not only recognize a number of specific components conserved among microorganisms, but are also capable of recognizing specific defensins as well as fragments of extracellular matrix proteins [1][2][3][4][5][6][7]. Since, the activation of macrophages or dendritic cells (DCs) through one or more of their TLRs enhances innate immunity and can modulate the subsequent development of antigen-specific adaptive immunity, some TLR ligands have been used as adjuvants in vaccine formulations administered parenterally to augment systemic immune responses [8][9][10][11]. Specific TLR ligands have been reported to promote the induction of both systemic and mucosal immune responses when co-administered with antigen intranasally [9][10][11][12].*Corresponding author. Address: Department of Pathology, University of Utah Medical School, 30 North 1900 East, Salt Lake City, UT 84132, USA; Phone: 1-801-585-1522; Fax: 1-801-581-8946; e-mail: elena.enioutina@path.utah.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptVaccine. Author manuscript; available in PMC 2009 January 30. Published in final edited form as:Vaccine. We have previously demonstrated that the subcutaneous or intradermal imm...

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1,25‐Dihydroxyvitamin D3 Enhances Systemic and Mucosal Immune Responses to Inactivated Poliovirus Vaccine in Mice

Cited by 61 publications

References 9 publications

Efficient tetanus toxoid immunization on vitamin D supplementation

Efficient tetanus toxoid immunization on vitamin D supplementation

Epidemiologic evidence for supporting the role of maternal vitamin D deficiency as a risk factor for the development of infantile autism

TLR ligands that stimulate the metabolism of vitamin D3 in activated murine dendritic cells can function as effective mucosal adjuvants to subcutaneously administered vaccines

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