New malaria vaccine candidates based on the Plasmodium vivax Merozoite Surface Protein-1 and the TLR-5 agonist Salmonella Typhimurium FliC flagellin

Bargieri, Daniel Youssef; Rosa, Daniela Santoro; Braga, Catarina Joelma Magalhães; Carvalho, Bruna O.; Costa, Fábio T. M.; Espíndola, Noeli Maria; Vaz, Adelaide José; Soares, Irene S.; Ferreira, Luís Carlos de Souza; Rodrigues, Maurício M.

doi:10.1016/j.vaccine.2008.08.070

Cited by 119 publications

(108 citation statements)

References 67 publications

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“…Consistent with this, a number of studies showed that flagellin has adjuvant-like properties (17,18) Vaccination with recombinant flagellin-Ag fusions induced potent T and B cell responses, including Ag-specific CD8 + T cell and Ab responses to model Ags (19,20), as well as to a number of disease-relevant Ags (21)(22)(23), including influenza M2e Ag (24), Plasmodium vivax merozoite surface protein-1 (25), and Mycobacterium tuberculosis Ag p27 (26). The responses induced were often much greater than those induced by vaccination of the Ag emulsified in CFA (20)(21)(22)(23)(24)(25)(26). Also, the linking of flagellin to Ag is essential to induce detectable Ab responses, because a simple mixing of the two is not sufficient (20)(21)(22)(23)(24)(25)(26).…”

mentioning

confidence: 69%

Antigen-Containing Liposomes Engrafted with Flagellin-Related Peptides Are Effective Vaccines That Can Induce Potent Antitumor Immunity and Immunotherapeutic Effect

Faham

Altin

2010

The Journal of Immunology

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mentioning

confidence: 69%

Antigen-Containing Liposomes Engrafted with Flagellin-Related Peptides Are Effective Vaccines That Can Induce Potent Antitumor Immunity and Immunotherapeutic Effect

Faham

Altin

2010

The Journal of Immunology

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“…116 As described above, as a consequence of the potent effects of flagellin on both the innate and adaptive limbs of the immune system, the protein has indeed been demonstrated to have potent adjuvantic effects in experimental vaccine constructs. [117][118][119][120][121][122] However, the safety profile of flagellin is yet to be unequivocally established. Of particular note, it has been observed that the administration of flagellin at doses comparable to or lower than that of bacterial LPS induces prominent local and systemic immune/inflammatory responses in vivo.…”

Section: Tlr5 Agonistic Flagellinmentioning

confidence: 99%

Potential adjuvantic properties of innate immune stimuli

et al. 2009

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Just as the prescient comment by Gaston Ramon was relegated to the last footnote of his 1926 paper, 1 so has research on the mechanisms of action of adjuvants, until recently, languished as parenthetical annotations and addenda in the archives of immunology and vaccine development. Ramon defined immunological adjuvants as "substances used in combination with a specific antigen that produced a more robust immune response than the antigen alone." Interestingly enough, he was referring to his empirical findings that the addition of bread crumbs, tapioca, saponin and 'starch oil' to antigenic preparations greatly enhanced antibody responses to diphtheria or tetanus. 2 A year later, the adjuvanticity of aluminum salts (primarily phosphate and hydroxide) was discovered by Glenny and coworkers. 3 In the 83 years that have elapsed, the repertoire of investigational adjuvants has grown to encompass a very wide range of materials, 4 but aluminum salt-based mineral salts (generically, and incorrectly, termed "alum") have remained the only adjuvants currently approved by the FDA. Aluminum salts have enjoyed a good safety record, but they are weak adjuvants for antibody induction and induce a T helper-2 (T H 2)-skewed, rather than a T helper-1 (T H 1) response. 5,6 Furthermore, not only are aluminum salts ineffective at inducing cytotoxic T lymphocyte (CTL) or mucosal IgA antibody responses, but also have a propensity to induce IgE responses, which have been associated with allergic reactions in some subjects. 5,6 Very recent reports implicate the Nalp3 inflammasome, a component of the innate immune response, as the effector limb of alum-associated adjuvanticity. [7][8][9] In 1962, Dresser observed that injection of purified soluble proteins not only failed to stimulate an immune response, but tolerized animals unless a bacterial extract was admixed with the protein immunogen. 10 This led him to redefine adjuvanticity as "a property of a substance which can act as a physiological switch, directing at least some immunologically competent cells to respond by making antibody rather than by becoming immunologically paralyzed by the antigen," 11 confirming Johnson's earlier observations that lipopolysaccharide (LPS) from Gram-negative bacteria exerted potent adjuvant properties, 12 and perhaps paved the way for the subsequent discovery of the wide range of microorganism-derived adjuvants. 13 TLRs are pattern recognition receptors present on diverse cell types that recognize specific molecular patterns present in molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs). 14,15 There are 10 TLRs in the human genome;

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“…78,79 Two recent studies have demonstrated the capacity of these new mucosal adjuvants for delivery of malaria vaccines. 80,81 In one study, intranasal immunization with P. vivax MSP1 19 , in the presence of S. typhimurium flagellin either admixed or genetically linked, elicited strong and long-lasting MSP1 19 -specific systemic antibodies. 81 In the second study, a synthetic peptide of 69 amino acids from the C-terminal domain of P. berghei CSP was able to induce complete protection against sporozoite challenge when administered intranasally with a modified LT (LTK63).…”

Section: Alternative Delivery Methods For Malaria Vaccinesmentioning

confidence: 99%

“…80,81 In one study, intranasal immunization with P. vivax MSP1 19 , in the presence of S. typhimurium flagellin either admixed or genetically linked, elicited strong and long-lasting MSP1 19 -specific systemic antibodies. 81 In the second study, a synthetic peptide of 69 amino acids from the C-terminal domain of P. berghei CSP was able to induce complete protection against sporozoite challenge when administered intranasally with a modified LT (LTK63). 80 LTK63 is a genetically detoxified derivative of LT, which has been tested in a Phase I clinical trial as a mucosal adjuvant for intranasally delivered trivalent influenza vaccine.…”

Section: Alternative Delivery Methods For Malaria Vaccinesmentioning

confidence: 99%