Intranasal Cry1Ac Protoxin is an Effective Mucosal and Systemic Carrier and Adjuvant of <i>Streptococcus pneumoniae</i> Polysaccharides in Mice

Moreno‐Fierros, Leticia; Ruiz-Medina, E J; Esquivel, Rita; López‐Revilla, Rubén; Piña-Cruz, S

doi:10.1046/j.1365-3083.2003.01190.x

Cited by 45 publications

(41 citation statements)

References 57 publications

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“…Our group has found that the Cry1Ac protoxin from B. thuringiensis is highly immunogenic and has mucosal and systemic adjuvant effects when administered to mice by systemic and mucosal routes (25,26,33,34). However, the protoxin had not been tested to determine whether coadministration of Cry1Ac with antigens could increase protective immunity in a mucosal infection model.…”

Section: Discussionmentioning

confidence: 99%

“…Our group has reported that the Cry1Ac protoxin of Bacillus thuringiensis is highly immunogenic (25,33) and has mucosal and systemic adjuvant effects, since it increases specific antibody responses to proteins such as bovine serum albumin and the hepatitis B surface antigen (34), and to polysaccharides such as the type 6 capsular pneumococcal polysaccharide and a polyvalent pneumococcal polysaccharide vaccine (26). Cry1Ac has additional advantages over other mucosal adjuvants (16,30): it is nontoxic to vertebrates, and its production costs are low (13,14).…”

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confidence: 99%

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Intranasal Coadministration of the Cry1Ac Protoxin with Amoebal Lysates Increases Protection againstNaegleria fowleriMeningoencephalitis

et al. 2004

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Cry1Ac protoxin has potent mucosal and systemic adjuvant effects on antibody responses to proteins or polysaccharides. In this work, we examined whether Cry1Ac increased protective immunity against fatal Naegleria fowleri infection in mice, which resembles human primary amoebic meningoencephalitis. Higher immunoglobulin G (IgG) than IgA anti-N. fowleri responses were elicited in the serum and tracheopulmonary fluids of mice immunized by the intranasal or intraperitoneal route with N. fowleri lysates either alone or with Cry1Ac or cholera toxin. Superior protection against a lethal challenge with 5 ؋ 10 4 live N. fowleri trophozoites was achieved for immunization by the intranasal route. Intranasal immunization of N. fowleri lysates coadministered with Cry1Ac increased survival to 100%; interestingly, immunization with Cry1Ac alone conferred similar protection to that achieved with amoebal lysates alone (60%). When mice intranasally immunized with Cry1Ac plus lysates were challenged with amoebae, both IgG and IgA mucosal responses were rapidly increased, but only the increased IgG response persisted until day 60 in surviving mice. The brief rise in the level of specific mucosal IgA does not exclude the role that this isotype may play in the early defense against this parasite, since higher IgA responses were detected in nasal fluids of mice intranasally immunized with lysates plus either Cry1Ac or cholera toxin, which, indeed, were the treatments that provided the major protection levels. In contrast, serum antibody responses do not seem to be related to the protection level achieved. Both acquired and innate immune systems seem to play a role in host defense against N. fowleri infection, but further studies are required to elucidate the mechanisms involved in protective effects conferred by Cry1Ac, which may be a valuable tool to improve mucosal vaccines.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Intranasal Coadministration of the Cry1Ac Protoxin with Amoebal Lysates Increases Protection againstNaegleria fowleriMeningoencephalitis

et al. 2004

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“…Vazquez-Padron et al, 1999;Moreno-Fierros et al, 2003;RojasHernandez et al, 2004). However, at present, there is no evidence for Bt protein adjuvanticity of safety concern among the GM plants assessed so far by the EFSA GMO Panel (EFSA, 2009a; EFSA GMO Panel, 2011b, c).…”

Section: Assessment Of Allergenicity Of the Newly Expressed Proteinsmentioning

confidence: 99%

Scientific Opinion on applications (EFSA-GMO-UK-2008-57 and EFSA-GMO-RX-MON15985) for the placing on the market of insect-resistant genetically modified cotton MON 15985 for food and feed uses, import and processing, and for the renewal of authorisation o

Arpaia¹,

Birch²,

Chesson³

et al. 2014

EFSA Journal

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Cotton MON 15985 was developed by biolistic transformation of cotton MON 531 to express Cry2Ab2 and GUS in addition to the Cry1Ac and NPTII proteins. Cry proteins in MON 15985 confer resistance to major lepidopteran cotton pests, whereas the GUS and NPTII proteins were used as markers during product development. Molecular characterisation of MON 15985 did not give rise to safety issues. The EFSA GMO Panel could not conclude on the potential occurrence of unintended effects for agronomic and phenotypic characteristics owing to data limitations. Compositional data gave no indication of unintended effects for which further assessment was needed. The Panel concludes that cotton MON 15985, as described in these applications, is as safe and nutritious as its conventional counterpart and other non-genetically modified varieties, and considers it unlikely that the overall allergenicity of the whole plant is changed. Environmental risk assessment was restricted to the exposure through faecal material from animals fed with cotton products of MON 15985 and its accidental spillage. Following a weight of evidence approach and considering the poor ability of cotton to survive outside cultivated land, despite the agronomic and phenotypic data limitations, the Panel concludes that there is very low likelihood of any adverse environmental impacts. The aadA and oriV sequences in MON 15985 may facilitate the stabilisation of nptII through double homologous recombination. However, considering the limited presence of intact DNA from MON 15985 in feed and the limited occurrence of horizontal transfer of DNA from plant material to bacteria, the Panel concludes that it is highly unlikely that nptII from MON 15985 will be transferred to bacteria. Since both EFSA-GMO-UK-2008-57 and EFSA-GMO-RX-MON15985 cover cotton MON 15985, the EFSA GMO Panel provides a single scientific opinion, valid for both applications.The EFSA GMO Panel evaluated cotton MON 15985 with reference to the scope and appropriate principles described in its guidance documents for the risk assessment of genetically modified (GM) plants and derived food and feed (EFSA, 2006a; EFSA GMO Panel, 2011a), environmental risk assessment (ERA) (EFSA GMO Panel, 2010a) and for renewal of authorisations of existing GMO products lawfully placed on the market (EFSA, 2006b). The scientific evaluation of the risk assessment included molecular characterisation of the inserted DNA and analysis of the expression of the corresponding proteins. An evaluation of the comparative analyses of compositional, agronomic and phenotypic characteristics was undertaken, and the safety of the newly expressed proteins and the whole food/feed was evaluated with respect to potential toxicity, allergenicity and nutritional wholesomeness. An evaluation of environmental impacts and the post-market environmental monitoring (PMEM) plan was also undertaken.The scope of applications EFSA-GMO-UK-2008-57 and EFSA-GMO-RX-MON15985 covers the MON 15985 event in cotton species Gossypium hirsutum L. and G. barba...

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“…hepatitis B surface antigen or the capsular polysaccharide of Streptococcus pneumoniae, where co-administered with the Cry protein through the i.g., i.p., and i.n. routes Moreno-Fierros et al, 2003). The EFSA GMO Panel is of the opinion that, as maize is not a common allergenic food, the adjuvant effect of Cry proteins, observed after high dosage intragastric or intranasal administration, is unlikely to raise any concerns regarding allergenicity.…”

Section: Assessment Of Allergenicity Of the Newly Expressed Proteinsmentioning

confidence: 99%

Application (Reference EFSA-GMO-UK-2005-11) for the placing on the market of insect-resistant genetically modified maize MIR604 event, for food and feed uses, import and processing under Regulation (EC) No 1829/2003 from Syngenta Seeds S.A.S on behalf of

Andersson¹,

Arpaia²,

Bartsch³

et al. 2009

EFSA Journal

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SUMMARYFollowing a request from Syngenta Seeds S.A.S on behalf of Syngenta Crop Protection AG within the framework of Regulation (EC) No 1829/2003 on genetically modified food and feed, the Panel on Genetically Modified Organisms of the European Food Safety Authority (EFSA GMO Panel) was asked to deliver a scientific opinion on the authorisation of the insect-resistant genetically modified maize MIR604 (Unique Identifier SYN-IR6Ø4-5) for food and feed uses, import and processing.In delivering its scientific opinion, the EFSA GMO Panel considered the new application EFSA-GMO-UK-2005-11, additional information provided by the applicant and the scientific comments submitted by the Member States. The scope of application EFSA-GMO-UK-2005-11 is for food and feed uses, import and processing of genetically modified maize MIR604 and all derived products, but excluding cultivation in the EU.The EFSA GMO Panel assessed maize MIR604 with reference to the intended uses and appropriate principles described in the Guidance Document of the Scientific Panel on Genetically Modified Organisms for the risk assessment of genetically modified plants and derived food and Insect-resistant GM maize MIR604 for food and feed uses, import and processingThe EFSA Journal (2009) 1193, 2-26 feed. The scientific assessment included molecular characterisation of the inserted DNA and expression of the newly expressed proteins. A comparative analysis of agronomic traits and composition was undertaken, and the safety of the new proteins and the whole food/feed were evaluated with respect to potential toxicity, allergenicity and nutritional quality. An assessment of environmental impacts and the post-market environmental monitoring plan was also undertaken.Maize MIR604 was engineered with a modified cry3A coding sequence (mcry3A) derived from Bacillus thuringiensis subsp. tenebrionis that encodes an insecticidally active mCry3A protein confering resistance to the Western Corn rootworm (WCR) (Diabrotica virgifera virgifera) and other related coleopteran pests of maize like the Northern Corn rootworm (NCR) (Diabrotica barberi). In addition maize MIR604 was engineered with the pmi (manA) gene from Escherichia coli, which encodes the enzyme PMI (PhosphoMannose Isomerase) as a selectable marker. PMI allows transformed maize cells to utilize mannose as a sole carbon source, while maize cells lacking the pmi gene fail to grow with mannose as single carbon source.The molecular characterisation data established that a single insert with one copy of the expression cassette containing the mCry3A gene and the pmi gene is integrated in the maize genomic DNA. Appropriate analyses of the integration site including sequence determination of the inserted DNA and flanking regions. Bioinformatic analysis of junction regions demonstrated the absence of any potential new ORFs coding for known toxins or allergens. The expression of the gene introduced by genetic modification has been sufficiently analysed and the stability of the genetic modification has been demonstra...

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Intranasal Cry1Ac Protoxin is an Effective Mucosal and Systemic Carrier and Adjuvant of Streptococcus pneumoniae Polysaccharides in Mice

Cited by 45 publications

References 57 publications

Intranasal Coadministration of the Cry1Ac Protoxin with Amoebal Lysates Increases Protection againstNaegleria fowleriMeningoencephalitis

Intranasal Coadministration of the Cry1Ac Protoxin with Amoebal Lysates Increases Protection againstNaegleria fowleriMeningoencephalitis

Scientific Opinion on applications (EFSA-GMO-UK-2008-57 and EFSA-GMO-RX-MON15985) for the placing on the market of insect-resistant genetically modified cotton MON 15985 for food and feed uses, import and processing, and for the renewal of authorisation o

Application (Reference EFSA-GMO-UK-2005-11) for the placing on the market of insect-resistant genetically modified maize MIR604 event, for food and feed uses, import and processing under Regulation (EC) No 1829/2003 from Syngenta Seeds S.A.S on behalf of

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