Local cytokine and inflammatory responses to candidate vaginal adjuvants in mice

Lindqvist, Madelene; Navabi, Nazanin; Jansson, Marianne; Samuelson, Emma; Sjöling, Åsa; Örndal, Charlotte; Harandi, Ali M.

doi:10.1016/j.vaccine.2009.09.083

Cited by 13 publications

(12 citation statements)

References 24 publications

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“…Ifng gene was identified as the main inducer of the inflammatory pathway induced by both adjvuvants, while Tnfa, Il6 and Il1b genes were solely up-regulated by CpG [31]. The excessive inflammatory response induced in the vaginal mucosa by CpG may explain the previously observed damage to the vaginal epithelium by CpG [34]. Furthermore, ␣-GalCer, but not CpG, induced up regulation of genes involved in inhibitory receptor programmed death 1 (PD-1) signaling that has been shown to be involved in controlling excessive inflammation [35].…”

Section: Mode Of Actions Of Exploratory Mucosal Adjuvantsmentioning

confidence: 92%

Molecular signatures of vaccine adjuvants

Olafsdottir

Lindqvist

Harandi

2015

Vaccine

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Mass vaccination has saved millions of human lives and improved the quality of life in both developing and developed countries. The emergence of new pathogens and inadequate protection conferred by some of the existing vaccines such as vaccines for tuberculosis, influenza and pertussis especially in certain age groups have resulted in a move from empirically developed vaccines toward more pathogen tailored and rationally engineered vaccines. A deeper understanding of the interaction of innate and adaptive immunity at molecular level enables the development of vaccines that selectively target certain type of immune responses without excessive reactogenicity. Adjuvants constitute an imperative element of modern vaccines. Although a variety of candidate adjuvants have been evaluated in the past few decades, only a limited number of vaccine adjuvants are currently available for human use. A better understanding of the mode of action of adjuvants is pivotal to harness the potential of existing and new adjuvants in shaping a desired immune response. Recent advancement in systems biology powered by the emerging cutting edge omics technology has led to the identification of molecular signatures rapidly induced after vaccination in the blood that correlate and predict a later protective immune response or vaccine safety. This can pave ways to prospectively determine the potency and safety of vaccines and adjuvants. This review is intended to highlight the importance of big data analysis in advancing our understanding of the mechanisms of actions of adjuvants to inform rational development of future human vaccines.

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Section: Mode Of Actions Of Exploratory Mucosal Adjuvantsmentioning

confidence: 92%

Molecular signatures of vaccine adjuvants

Olafsdottir

Lindqvist

Harandi

2015

Vaccine

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“…Excessive and long-lasting proinflammatory responses in the mucosa may lead to tissue damage, which in turns promotes secondary infections. For example, intravaginal administration of unmethylated CpG oligonucleotides (CpG ODNs), has been shown to cause severe damage to the vaginal epithelium, and this may lead to an increase in the acquisition of sexually transmitted infections, for example: the human immunodeficiency virus Type 1 (HIV-1) [103].…”

Section: Considerations Regarding Inoculation Routesmentioning

confidence: 99%

“…It is known that antimicrobial defensive measures including the production of inflammatory cytokines (i.e., IL-1, IL-6, and TNF-alpha), antimicrobial peptides and neutrophil chemoattractants, are favored by TLR signals mediated by a MyD88-dependent pathway. Partial TLR agonist adjuvants such as: GalCer [103] and monophosphoryl lipid A (MPL) [115], however, can induce co-stimulation through a MyD88-independent pathway that uses the TRIF/TRAM protein complex and prevents excessive inflammation [7]. These findings have implications for the development of safer adjuvants.…”

Section: Local Toxicity and Adjuvanticitymentioning

confidence: 99%

An approach to local immunotoxicity induced by adjuvanted vaccines

Batista-Duharte¹,

Portuondo

Carlos

et al. 2013

International Immunopharmacology

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“…Administering a single dose of CpG ODN intravaginally resulted in the rapid upregulation of more inflammatory cytokine genes than did αGalCer, as the latter induced a delayed and more transient pattern of gene expression (Lindqvist et al, 2011). Yet CpG ODN, but not αGalCer, induced massive inflammatory cell infiltration of the vagina, resulting in damage to the vaginal epithelium (an effect that reversed by 48 h (Lindqvist et al, 2009)). These results suggest that while more potent than αGalCer, the proinflammatory response induced by CpG ODN may damage vaginal epithelium, making this adjuvant unsuitable for that route of application.…”

Section: Cpg Versus α-Galactosylceramide (αGalcer)mentioning

confidence: 99%