Antibody responses in adult and neonatal BALB/c mice to immunization with novel Bordetella pertussis vaccine formulations

Gracia, Aleksandra; Polewicz, Monika; Halperin, Scott A.; Hancock, Robert E. W.; Potter, Andrew; Babiuk, Lorne A.; Gerdts, Volker

doi:10.1016/j.vaccine.2010.12.083

Cited by 53 publications

(28 citation statements)

References 37 publications

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“…Anti-infective peptides IDR-1 and IDR-1002 confer in vivo protection against bacterial infections through modulation of innate immune responses, including the regulation of chemokine/cytokine responses and recruitment of monocytes to the site of infection [3,4]. Likewise, IDR-1018 and IDR-HH2 also demonstrate the ability to modulate the host cytokine/chemokine environment [26,27], while both IDR-1002 and IDR-HH2 promote adjuvant activity in formulation [5,6]. We sought to determine whether the ability to promote monocyte adhesion to fibronectin demonstrated by IDR-1002 was shared with other IDR peptides as well.…”

Section: Resultsmentioning

confidence: 99%

“…It has also been developed and outlicensed as a component of an adjuvant formulation, comprising IDR-1002, CpG oligonucleotide and polyphosphazene. In this adjuvant formulation, which enables effective single-dose vaccines against pertussis, its primary role is to enhance recruitment of immune cells [5,6]. Although IDR peptides demonstrate potent anti-infective and adjuvant properties, our limited understanding regarding the mechanisms by which IDR peptides modulate immunity represents an obstacle in their development as clinical therapeutic agents.…”

Section: Introductionmentioning

confidence: 99%

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Synthetic Immunomodulatory Peptide IDR-1002 Enhances Monocyte Migration and Adhesion on Fibronectin

Madera

Hancock²

2012

J Innate Immun

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Regulation of the immune system by immunomodulatory agents, such as the synthetic innate defense regulator (IDR) peptides, has been proposed as a potential strategy to strengthen host immune responses against infection. IDR peptides confer protection in vivo against a range of bacterial infections and have been developed as components of single-dose vaccine adjuvants due to their ability to modulate innate immunity, correlating with an increased recruitment of monocytes to sites of infection or immunization. However, the mechanisms by which IDR peptides augment monocyte recruitment remain poorly defined. Anti-infective peptide IDR-1002 was demonstrated here to lack direct monocyte chemoattractive activity yet enhance, by up to 5-fold, the ability of human monocytes to migrate on fibronectin towards chemokines. This effect correlated with an increased adhesion of monocytes and THP-1 cells to fibronectin by IDR-1002 and other IDR peptides and the adhesion of THP-1 cells to fibronectin occurred in a β₁-integrin-dependent manner, corresponding with an increased activation of β₁-integrins and the phosphoinositide 3-kinase (PI3K)-Akt pathway. PI3K- and Akt-specific inhibitors abrogated IDR-1002-induced adhesion and activation of β₁-integrins, whereas p38 and MEK1 inhibitors did not affect, or moderately inhibited, adhesion, respectively. Furthermore, IDR-1002 enhancement of monocyte migration towards chemokines and activation of β₁-integrins was abrogated in the presence of PI3K- and Akt-specific inhibitors. In summary, IDR-1002 enhanced monocyte migration on fibronectin through promotion of β₁-integrin-mediated interactions regulated by the PI3K-Akt pathway, revealing a mechanism by which IDR-1002 promotes monocyte recruitment.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthetic Immunomodulatory Peptide IDR-1002 Enhances Monocyte Migration and Adhesion on Fibronectin

Madera

Hancock²

2012

J Innate Immun

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“…This indicates that the impact an adolescent booster would have on infant pertussis is yet to be determined. However, further development of acellular pertussis vaccines, e.g., with additional antigens (47,48) or adjuvants (49,50), could lead to better efficacy of the adolescent booster and thus induction of sustainable protection into the childbearing years. Studies have shown that whole-cell pertussis vaccines seem to offer better protection than acellular vaccines (51,52).…”

Section: Discussionmentioning

confidence: 99%

Pertussis-Specific Memory B-Cell and Humoral IgG Responses in Adolescents after a Fifth Consecutive Dose of Acellular Pertussis Vaccine

Jahnmatz¹,

Ljungman²,

Netterlid³

et al. 2014

Clin. Vaccine Immunol.

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In order to impede the increase in pertussis incidence in the adolescent group, a school-leaving booster dose administered at the age of 14 to 16 years will be introduced in Sweden in 2016. Preceding this introduction, an open-label, randomized, multicenter, clinical trial without a control group and with blinded analysis was performed, investigating both safety and immunogenicity. Reported here are the memory B-cell and serological responses detected in a smaller cohort (n ‫؍‬ 34) of the 230 subjects recruited to the study. All subjects had received primary vaccination consisting of three doses of diphtheria-tetanus-5-component pertussis (DTaP5) vaccine, at 3, 5, and 12 months of age, and a tetanus-low-dose diphtheria-5-component pertussis (Tdap5) vaccine booster at 5.5 years. In this study, the subjects were randomly assigned and received either a Tdap1 or Tdap5 booster. Of the 230 participants, 34 subjects had samples available for evaluation of IgG-producing memory B-cell responses. Both vaccine groups had significant increases in pertussis toxin-specific serum IgG levels, but only the 1-component group showed significant increases in pertussis toxin-specific memory B cells. The 5-component group had significant increases in filamentous hemagglutinin-and pertactin-specific memory B-cell and serum IgG levels; these were not seen in the 1-component group, as expected. In conclusion, this study shows that a 5th consecutive dose of an acellular pertussis vaccine induces B-cell responses in vaccinated adolescents. (This study has been registered at EudraCT under registration no. 2008-008195-13 and at ClinicalTrials.gov under registration no. NCT00870350.)

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“…However, aluminum hydroxide (Alum) is an appropriate vehicle for the retention/sustained delivery of early-life immunomodulators. TLR agonists delivered with aluminum salts increase early-life murine Ab responses (8,10,11). For example, monophosphoryl lipid A, a TLR4 ligand, synergizes with aluminum salts to improve B cell responses to hepatitis B and HPV vaccines (12).…”

mentioning

confidence: 99%

IL-36–Induced Toxicity in Neonatal Mice Involves TNF-α Production by Liver Myeloid Cells

Palomo

Mastelic-Gavillet

Woldt

et al. 2016

The Journal of Immunology

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Human and mouse neonates exhibit limited vaccine responses characterized by predominant Th2 and limited Th1 responses. Because IL-36 exerts a synergic adjuvant effect with IL-12, enhancing Th1 polarization in adult (AD) mice, we administered IL-36β to neonatal (1-wk old) and AD control mice at the time of immunization with tetanus toxoid adsorbed to aluminum hydroxide (TT/Alum). Unexpectedly, the combination of IL-36β with TT/Alum, which was well tolerated in AD mice, proved toxic and even lethal in neonates. This neonatal toxicity was associated with high Il36r mRNA expression in neonatal liver, resulting in increased cytokine production. Liver Il36r mRNA expression decreased with the termination of fetal liver hematopoiesis, and this decrease correlated with a complete protection from TT/Alum/IL-36β–induced mortality. The combination of IL-36β and TT/Alum induced the rapid production of TNF-α and IFN-γ by liver myeloid and lymphoid cells, respectively. These responses were less marked when IL-36β was used alone, with no adverse effect. The toxicity of IL-36β + TT/Alum was abrogated by the administration of a neutralizing anti–TNF-α Ab, confirming causality. In conclusion, liver myeloid cells in neonatal mice are an important source of proinflammatory cytokines that may lead to TNF-α–mediated toxicity and even lethality.

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Antibody responses in adult and neonatal BALB/c mice to immunization with novel Bordetella pertussis vaccine formulations

Cited by 53 publications

References 37 publications

Synthetic Immunomodulatory Peptide IDR-1002 Enhances Monocyte Migration and Adhesion on Fibronectin

Synthetic Immunomodulatory Peptide IDR-1002 Enhances Monocyte Migration and Adhesion on Fibronectin

Pertussis-Specific Memory B-Cell and Humoral IgG Responses in Adolescents after a Fifth Consecutive Dose of Acellular Pertussis Vaccine

IL-36–Induced Toxicity in Neonatal Mice Involves TNF-α Production by Liver Myeloid Cells

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