Human immune responses to influenza virus vaccines administered by systemic or mucosal routes

Moldoveanu, Zina; Clements, Mary Lou; Prince, Shirley J.; Murphy, B R; Městecký, Jiří

doi:10.1016/0264-410x(95)00016-t

Cited by 176 publications

(130 citation statements)

References 29 publications

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“…Our results on antibody responses in the NALT tissue induced by LAIV and the inactivated sH1N1 antigen are in general consistent with previous findings that intranasally administered LAIV induced prominent antibody responses including IgA and IgG in nasal lavage mucosal samples (Moldoveanu et al, 1995), and the inactivated antigen elicits primarily an IgG-predominant memory response (Bentebibel et al, 2013). Given that many subjects would have been exposed previously to infection of various strains of influenza viruses, it is plausible that these previous contact induced memory and would to some degree have impact on the antibody response tested in this study.…”

Section: P a G Esupporting

confidence: 92%

A critical role of T follicular helper cells in human mucosal anti-influenza response that can be enhanced by immunological adjuvant CpG-DNA

et al. 2016

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Section: P a G Esupporting

confidence: 92%

A critical role of T follicular helper cells in human mucosal anti-influenza response that can be enhanced by immunological adjuvant CpG-DNA

et al. 2016

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“…Nasal administration of live attenuated influenza vaccine in humans has also produced specific IgA Ab in saliva (28). We now have extended these findings to show that N imm can also induce distal Ag-specific IgA in rectal secretions of humans.…”

Section: Discussionmentioning

confidence: 58%

“…High proportions of influenza-specific IgA Ab have been generated in saliva after N imm of humans with live attenuated flu vaccine (28). N imm may be more effective for induction of salivary Ab in previously primed individuals or by administering replication-competent vaccines.…”

Section: Discussionmentioning

confidence: 99%

Differential Induction of Mucosal and Systemic Antibody Responses in Women After Nasal, Rectal, or Vaginal Immunization: Influence of the Menstrual Cycle

Kozlowski

Williams²,

Lynch³

et al. 2002

The Journal of Immunology

205

186

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A cholera vaccine containing killed vibrios and cholera toxin B subunit (CTB) was used to compare mucosal immunization routes for induction of systemic and mucosal Ab. Four groups of women were given three monthly immunizations by the rectal immunization (Rimm) route, nasal immunization (Nimm) route, or vaginal immunization route during either the follicular (V-FPimm) or luteal (V-LPimm) menstrual cycle phase. Nimm was performed with 10-fold less vaccine to determine if administration of less Ag by this route can, as in rodents, produce mucosal Ab responses comparable to those induced by higher dose Rimm or vaginal immunization. Concentrations of Ab induced in sera and secretions were measured by ELISA. None of these routes produced durable salivary Ab responses. Nimm induced greatest levels of CTB-specific IgG in sera. Rimm failed to generate CTB-specific IgA in genital tract secretions. Nimm, V-FPimm, and V-LPimm all produced cervical CTB-specific IgA responses comparable in magnitude and frequency. However, only V-FPimm induced cervical IgA2-restricted Ab to the bacterial LPS vaccine component. V-FPimm, but not V-LPimm, also induced CTB-specific IgA in rectal secretions. Nimm was superior to V-FPimm for producing rectal CTB-specific IgA, but the greatest amounts of CTB-specific IgA and LPS-specific IgA, IgG, and IgM Ab were found in rectal secretions of Rimm women. These data suggest that in women, Nimm alone could induce specific Ab in serum, the genital tract, and rectum. However, induction of genital tract and rectal Ab responses of the magnitude generated by local V-FPimm or Rimm will likely require administration of comparably high nasal vaccine dosages.

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“…Some evidence suggests that lumenal IgG represents passive transudation from the serum. This view is challenged by studies that show that numbers of local IgG-secreting cells in mucosal tissues and levels of antigen-specific IgG in mucosal secretions can be dramatically increased after both mucosal and systemic immunization (54)(55)(56)(57)(58)(59)(60). In addition, Berneman et al (57) have found that the patterns of IgG subclasses in human serum differ from those found in autologous secretions at mucosal surfaces, and demonstrate that the concentration of IgG subclasses differ from those found in the serum.…”

Section: Discussionmentioning

confidence: 99%

Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell line

Dickinson¹,

Badizadegan²,

Wu³

et al. 1999

J. Clin. Invest.

399

361

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IntroductionSteady-state levels of IgG in the blood of adult mice, and likely all mammals, depend on IgG catabolism mediated in part by the MHC class I-related Fc receptor, FcRn (1). FcRn also mediates vectorial transport of IgG across certain epithelial barriers. In suckling mice and rats, intestinal absorption of maternal IgG from breast milk into the systemic circulation depends on FcRn (2). In humans, maternofetal transfer of IgG across the placenta also likely depends on FcRn (3). Thus, FcRn plays critical and well-documented roles in the regulation of IgG metabolism in adults and in the acquisition of humoral immunity in early life. These effects on the physiology of IgG in vivo result from the action of FcRn as an intracellular trafficking receptor (4).FcRn has been cloned from the rat, mouse, and human. The molecule is expressed as a heterodimer composed of a glycosylated heavy (α) chain (51 kDa in rodents and 40-45 kDa in humans) associated noncovalently with β2-microglobulin (β2M) (5). Binding of IgG to FcRn requires contact between solvent-exposed peptide sequences in the CH2 and CH3 domains of IgG and the α1 and α2 domains of FcRn, together with a single contact site in β2M (6-11). A hallmark of FcRn interaction with IgG is its pH dependence, showing high-affinity binding at acidic pH (pH ≤ 6.5) and weak or no binding at neutral pH (pH ≥ 7.0) (12, 13). FcRn is the only Fcγ receptor that exhibits MHC class I structure, and the only Fcγ receptor to exhibit pH dependency in ligand binding.The function of FcRn in the intestine of suckling mice and rats has been well documented (14). In neonatal mice and rats, FcRn is expressed at high levels by intestinal epithelial cells and mediates absorption of IgG by receptor-mediated transcytosis. FcRn expression in the neonatal rodent is developmentally downregulated, resulting in nearly complete loss of intestinal FcRn at the time of weaning (15)(16)(17) The MHC class I-related Fc receptor, FcRn, mediates the intestinal absorption of maternal IgG in neonatal rodents and the transplacental transport of maternal IgG in humans by receptor-mediated transcytosis. In mice and rats, expression of FcRn in intestinal epithelial cells is limited to the suckling period. We have recently observed, however, clear expression of FcRn in the adult human intestine, suggesting a function for FcRn in intestinal IgG transport beyond neonatal life in humans. We tested this hypothesis using the polarized human intestinal T84 cell line as a model epithelium. Immunocytochemical data show that FcRn is present in T84 cells in a punctate apical pattern similar to that found in human small intestinal enterocytes. Solute flux studies show that FcRn transports IgG across T84 monolayers by receptor-mediated transcytosis. Transport is bidirectional, specific for FcRn, and dependent upon endosomal acidification. These data define a novel bidirectional mechanism of IgG transport across epithelial barriers that predicts an important effect of FcRn on IgG function in immune surveillance and host de...

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Human immune responses to influenza virus vaccines administered by systemic or mucosal routes

Cited by 176 publications

References 29 publications

A critical role of T follicular helper cells in human mucosal anti-influenza response that can be enhanced by immunological adjuvant CpG-DNA

A critical role of T follicular helper cells in human mucosal anti-influenza response that can be enhanced by immunological adjuvant CpG-DNA

Differential Induction of Mucosal and Systemic Antibody Responses in Women After Nasal, Rectal, or Vaginal Immunization: Influence of the Menstrual Cycle

Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell line

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