A Phase 2b Controlled Efficacy Study of Intradermally Delivered ETEC Fimbrial Tip Adhesin Vaccine Against Experimental Challenge With ETEC H10407 in Healthy Adult Volunteers

The purpose of the study is to determine the efficacy of a vaccine against enterotoxigenic E. coli (ETEC)-caused diarrhea.

Start Date19 Sep 2013

Sponsor / Collaborator

U S Army Medical Research & Development Command

100 Clinical Results associated with LTR192G with dscCfaE(U.S. Army Medical Research and Development Command)

100 Translational Medicine associated with LTR192G with dscCfaE(U.S. Army Medical Research and Development Command)

100 Patents (Medical) associated with LTR192G with dscCfaE(U.S. Army Medical Research and Development Command)

Literatures (Medical) associated with LTR192G with dscCfaE(U.S. Army Medical Research and Development Command)

01 May 2020·VaccineQ3 · MEDICINE

A grading system for local skin reactions developed for clinical trials of an intradermal and transcutaneous ETEC vaccine

Q3 · MEDICINE

Article

Author: Riddle, Mark S ; Porter, Chad K ; Alcala, Ashley ; Turiansky, George W ; Jarell, Abel ; Gutiérrez, Ramiro L

BACKGROUNDTrials assessing the safety of novel vaccine candidates are essential in the evaluation and development of candidate vaccines. Immunogenicity and dose-sparing features of vaccination approaches which target skin and associated tissues have garnered increased interest; for enteric vaccines, cutaneous vaccination has been of particular interest. Cutaneous vaccine site reactions are among the most common and visible vaccine related adverse events (AEs) when skin routes are used. Regulatory guidelines governing classification of severity focus on functional impact but are insufficient to characterize a spectrum of skin reaction and allow for comparisons of routes, doses and products with similar local cutaneous AEs.OBJECTIVESOur group developed a grading scale to evaluate and compare cutaneous vaccine site reactions ahead of early-phase clinical trials of intradermal (ID) and transcutaneous immunization (TCI) with enterotoxigenic E.coli (ETEC) vaccine candidates (adhesin-based vaccine co-administered with LTR192G). We reviewed existing methods for characterizing the appearance and severity of local vaccine site reactions following TCI and ID vaccination and devised a standardized vaccine site appearance grading scale (VSAGS) for use in the clinical development of novel ETEC vaccine candidates which focused on pathophysiologic manifestation of skin findings.RESULTSAvailable data from published reports revealed erythematous papules and pruritus were the most common local AEs associated with TCI. Frequency of reactions varied notably across studies as did TCI vaccination methodologies and products. ID vaccination commonly results in erythema and induration at the vaccine site as well as pigmentation changes. There was no published methodology to characterize the spectrum of dermatologic findings.CONCLUSIONID and TCI vaccination are associated with a largely predictable range of cutaneous AEs. A grading scale focused on the appearance of cutaneous changes was useful in comparing cutaneous AEs. A standardized grading scale will facilitate documentation and comparison of cutaneous AEs.

01 Jan 2016·VaccineQ3 · MEDICINE

Immunogenicity of a prototype enterotoxigenic Escherichia coli adhesin vaccine in mice and nonhuman primates

Q3 · MEDICINE

Article

Author: Milagros Miller ; Aisling O’Dowd ; Eric R. Hall ; Stephen J. Savarino ; Colleen M. Woods ; Steven T. Poole ; Annette L. McVeigh ; Stephanie A. Sincock ; Nereyda Espinoza ; Gladys Nunez

Enterotoxigenic Escherichia coli (ETEC) are the most common cause of bacterial diarrhea in young children in developing countries and in travelers. Efforts to develop an ETEC vaccine have intensified in the past decade, and intestinal colonization factors (CFs) are somatic components of most investigational vaccines. CFA/I and related Class 5 fimbrial CFs feature a major stalk-forming subunit and a minor, antigenically conserved tip adhesin. We hypothesized that the tip adhesin is critical for stimulating antibodies that specifically inhibit ETEC attachment to the small intestine. To address this, we compared the capacity of donor strand complemented CfaE (dscCfaE), a stabilized form of the CFA/I fimbrial tip adhesin, and CFA/I fimbriae to elicit anti-adhesive antibodies in mice, using hemagglutination inhibition (HAI) as proxy for neutralization of intestinal adhesion. When given with genetically attenuated heat-labile enterotoxin LTR192G as adjuvant by intranasal (IN) or orogastric (OG) vaccination, dscCfaE exceeded CFA/I fimbriae in eliciting serum HAI titers and anti-CfaE antibody titers. Based on these findings, we vaccinated Aotus nancymaae nonhuman primates (NHP) with dscCfaE alone or admixed with one of two adjuvants, LTR192G and cholera toxin B-subunit, by IN and OG administration. Only IN vaccination with dscCfaE with either adjuvant elicited substantial serum HAI titers and IgA and IgG anti-adhesin responses, with the latter detectable a year after vaccination. In conclusion, we have shown that dscCfaE elicits robust HAI and anti-adhesin antibody responses in both mice and NHPs when given with adjuvant by IN vaccination, encouraging further evaluation of an ETEC adhesin-based vaccine approach.

01 Feb 2009·VaccineQ3 · MEDICINE

Spray-dried powders of starch and crosslinked poly(acrylic acid) as carriers for nasal delivery of inactivated influenza vaccine

Q3 · MEDICINE

Article

Author: Michael Schotsaert ; Claude Libert ; Jean Paul Remon ; Delphine Coucke ; P Foreman ; Chris Vervaet ; Xavier Saelens ; Eveline Pringels

Mucosal vaccination has several advantages over parenteral vaccination. In this study, viscosity-enhancing mucosal delivery systems for the induction of an adaptive immune response against viral antigen were investigated. Powder formulations based on spray-dried mixtures of starch (Amioca)/poly(acrylic acid) (Carbopol 974P) in different ratios were used as carriers of the viral antigen. A comparison of these formulations for intranasal delivery of heat-inactivated influenza virus combined with LTR192G adjuvant was made in vivo in a rabbit model. Individual rabbit sera were tested for seroconversion against hemagglutinin (HA), the major surface antigen of influenza. The powder vaccine formulations were able to induce systemic anti-HA IgG responses. The presence of Carbopol 974P improved the kinetics of the immune responses and the level of IgG titers in a dose-dependent way which was correlated with moderately irritating capacities of the formulation. In contrast, mucosal IgA responses were not detected. In conclusion, it was demonstrated that the use of bioadhesive carriers based on Amioca starch and poly(acrylic acid) facilitates the induction of a systemic anti-HA antibody response after intranasal vaccination with a whole virus influenza vaccine.

100 Deals associated with LTR192G with dscCfaE(U.S. Army Medical Research and Development Command)

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