Mucosal vaccines

Nizard, Mevyn; Diniz, Mariana O.; Roussel, H.; Tran, Thi; Ferreira, Luís Carlos de Souza; Badoual, Cécile; Tartour, Éric

doi:10.4161/hv.29269

Cited by 52 publications

(22 citation statements)

References 179 publications

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“…intranasal) and the presence of the so-called mucosal phenotype has been associated with strong anti-tumour protection 24 25 46 . In contrast to this hypothesis, we found that intralymphatically administered E7-TriMix vaccine exerted a therapeutic control on both lung lesions and genital tract lesions ( Figs 5 and 6 ), indicating that the vaccine-induced T cells can concentrate at the place where the antigen reservoir is available, even though they lacked the CD103 and CD49a expression and the vaccine was not given within the mucosal compartment 21 . In the same vein, some other groups report that—although CD103 is strongly indicative of tissue residence—it should be cautiously used as a definitive marker of Trm cells, since in many organs these cells lack CD103 expression 47 48 .…”

Section: Discussionmentioning

confidence: 63%

“…A growing body of evidence points to the existence of the so-called tissue resident memory cells (Trm)—a T cell population that permanently resides in peripheral tissues and does not enter the circulation. Therefore, in the context of mucosally located tumours it has been postulated that T cells could be generated in the process of imprinting, in which they are primed by dendritic cells derived from a mucosal tissue and thus endowed with the capacity to penetrate into and retain within this tissue 13 21 22 . Additionally, several convincing reports about the beneficial impact of Trm cells in the context of both infectious diseases and cancer exist 23 24 .…”

Section: Resultsmentioning

confidence: 99%

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Intralymphatic mRNA vaccine induces CD8 T-cell responses that inhibit the growth of mucosally located tumours

Bialkowski

Weijnen

Jeught

et al. 2016

Sci Rep

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The lack of appropriate mouse models is likely one of the reasons of a limited translational success rate of therapeutic vaccines against cervical cancer, as rapidly growing ectopic tumours are commonly used for preclinical studies. In this work, we demonstrate that the tumour microenvironment of TC-1 tumours differs significantly depending on the anatomical location of tumour lesions (i.e. subcutaneously, in the lungs and in the genital tract). Our data demonstrate that E7-TriMix mRNA vaccine-induced CD8+ T lymphocytes migrate into the tumour nest and control tumour growth, although they do not express mucosa-associated markers such as CD103 or CD49a. We additionally show that despite the presence of the antigen-specific T cells in the tumour lesions, the therapeutic outcomes in the genital tract model remain limited. Here, we report that such a hostile tumour microenvironment can be reversed by cisplatin treatment, leading to a complete regression of clinically relevant tumours when combined with mRNA immunization. We thereby demonstrate the necessity of utilizing clinically relevant models for preclinical evaluation of anticancer therapies and the importance of a simultaneous combination of anticancer immune response induction with targeting of tumour environment.

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Section: Discussionmentioning

confidence: 63%

Section: Resultsmentioning

confidence: 99%

Intralymphatic mRNA vaccine induces CD8 T-cell responses that inhibit the growth of mucosally located tumours

Bialkowski

Weijnen

Jeught

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The intranasal, as well as the bronchial epithelial cells are known to play a fundamental role in the airway defense mechanisms, and a critical role in mucosal immunity (Nizard et al, 2014) and are thus sites of interest for developing mucosal-based vaccines. Mucosal immune vaccination can activate both B and T cells which can drift to peripheral environmental, far distant from the one where the stimulation was induced (Meeusen, 2011).…”

Section: Discussionmentioning

confidence: 99%

Recombinant Invasive Lactococcus lactis Carrying a DNA Vaccine Coding the Ag85A Antigen Increases INF-γ, IL-6, and TNF-α Cytokines after Intranasal Immunization

et al. 2017

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Tuberculosis (TB) remains a major threat throughout the world and in 2015 it caused the death of 1.4 million people. The Bacillus Calmette-Guérin is the only existing vaccine against this ancient disease; however, it does not provide complete protection in adults. New vaccines against TB are eminently a global priority. The use of bacteria as vehicles for delivery of vaccine plasmids is a promising vaccination strategy. In this study, we evaluated the use of, an engineered invasive Lactococcus lactis (expressing Fibronectin-Binding Protein A from Staphylococcus aureus) for the delivery of DNA plasmid to host cells, especially to the mucosal site as a new DNA vaccine against tuberculosis. One of the major antigens documented that offers protective responses against Mycobacterium tuberculosis is the Ag85A. L. lactis FnBPA+ (pValac:Ag85A) which was obtained and used for intranasal immunization of C57BL/6 mice and the immune response profile was evaluated. In this study we observed that this strain was able to produce significant increases in the amount of pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6) in the stimulated spleen cell supernatants, showing a systemic T helper 1 (Th1) cell response. Antibody production (IgG and sIgA anti-Ag85A) was also significantly increased in bronchoalveolar lavage, as well as in the serum of mice. In summary, these findings open new perspectives in the area of mucosal DNA vaccine, against specific pathogens using a Lactic Acid Bacteria such as L. lactis.

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“…We and others clearly have shown that mucosal immunization was more efficient than the conventional systemic route (intramuscular, subcutaneous) to elicit Trm at the mucosal tumour site 19 20 21 22 . Indeed, the mucosal route of immunization imprints T cells with a mucosal homing programme defined by a profile of integrin and chemokine receptors promoting their homing to the site of initial activation 23 . A correlation was observed between the ability to elicit these cells at the tumour site and the control of tumour growth 24 .…”

mentioning

confidence: 99%

Induction of resident memory T cells enhances the efficacy of cancer vaccine

et al. 2017

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Tissue-resident memory T cells (Trm) represent a new subset of long-lived memory T cells that remain in tissue and do not recirculate. Although they are considered as early immune effectors in infectious diseases, their role in cancer immunosurveillance remains unknown. In a preclinical model of head and neck cancer, we show that intranasal vaccination with a mucosal vector, the B subunit of Shiga toxin, induces local Trm and inhibits tumour growth. As Trm do not recirculate, we demonstrate their crucial role in the efficacy of cancer vaccine with parabiosis experiments. Blockade of TFGβ decreases the induction of Trm after mucosal vaccine immunization, resulting in the lower efficacy of cancer vaccine. In order to extrapolate this role of Trm in humans, we show that the number of Trm correlates with a better overall survival in lung cancer in multivariate analysis. The induction of Trm may represent a new surrogate biomarker for the efficacy of cancer vaccine. This study also argues for the development of vaccine strategies designed to elicit them.

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Mucosal vaccines

Cited by 52 publications

References 179 publications

Intralymphatic mRNA vaccine induces CD8 T-cell responses that inhibit the growth of mucosally located tumours

Intralymphatic mRNA vaccine induces CD8 T-cell responses that inhibit the growth of mucosally located tumours

Recombinant Invasive Lactococcus lactis Carrying a DNA Vaccine Coding the Ag85A Antigen Increases INF-γ, IL-6, and TNF-α Cytokines after Intranasal Immunization

Induction of resident memory T cells enhances the efficacy of cancer vaccine

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