Recombinant Attenuated Salmonella Typhi Vaccine Vectors Producing Streptococcus Pneumoniae PspA

2014-08-27 03:17:13 | BioPortfolio


In this Phase I clinical study, three recombinant, avirulent Salmonella Typhi (RASV) strains each expressing the Streptococcus pneumoniae surface protein, PspA, will be compared as live biological vaccine vectors to evaluate safe and tolerable, single, oral dose levels in adult subjects.


The use of attenuated Salmonella strains that are unable to cause clinical disease but trigger a self-limiting infection leading to stimulation of protective immunity presents an attractive alternative to killed and subunit vaccines. Live, attenuated Salmonella strains have been shown to be excellent carriers, or vectors, for prokaryotic or eukaryotic antigens, being able to stimulate strong systemic and local immune responses against the expressed antigens. Three Salmonella Typhi strains have been engineered to express a gene encoding the alpha-helical domain of the Streptococcus pneumoniae surface protein, PspA, and will serve as live biological vaccine vectors in the proposed clinical trial to evaluate maximum safe and tolerable single dose levels after their oral administration to subjects. In this Phase I study, healthy young adults 18-40 years of age will participate in a dose escalating, dose sequential study divided into four Arms to receive doses of 10^7, 10^8, 10^9 and 10^10 CFU. Each Arm (1-4) will consist of 3 groups of 5 subjects per group to receive a single oral dose of one of three recombinant attenuated S. Typhi vaccine vectors producing the pneumococcal antigen PspA. Each group per Arm will receive the same dose of one of the three vaccines for a total of 60 subjects (15 subjects per dose-escalating Arm, 3 groups per Arm, 5 subjects per group). Subject participation lasts 6 months after receiving the oral vaccine dosage with approximately the first 12-15 days (study Days 0-14) in confinement. Release criteria include 2 negative blood cultures in a row through study Day 7 (inpatient monitoring for 8 days) and 2 negative stool cultures in a row through study Day 5. The objectives of the study are 1) to evaluate maximum safe tolerable single dose levels of the three recombinant attenuated S. Typhi vaccine vectors using dose-escalation, dose-sequential studies in healthy adult subjects, and 2) to evaluate immunogenicity of the three recombinant attenuated S. Typhi vaccine vectors with regard to their abilities to induce mucosal and systemic antibody responses to the S. pneumoniae PspA and S. Typhi antigens. The vaccines are not anticipated to prevent disease. Although the immune responses generated by the vaccine vectors may confer some degree of protection against future infection with S. pneumoniae and S. Typhi, such protection is incidental. It is not the goal of this study to develop or test either a pneumonia or typhoid vaccine, but to select the S. Typhi vector that provides optimal delivery of the PspA antigen in a safe and immunogenic manner.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science




Salmonella Typhi-vectored pneumonia vaccine, Salmonella Typhi-vectored pneumonia vaccine, Salmonella Typhi-vectored pneumonia vaccine, Salmonella Typhi-vectored pneumonia vaccine


Saint Louis University Center for Vaccine Development
St. Louis
United States




Arizona State University

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:17:13-0400

Clinical Trials [2658 Associated Clinical Trials listed on BioPortfolio]

Investigating Typhoid Fever Pathogenesis

Typhoid fever results from infection with a bacterium called Salmonella Typhi and is a major cause of illness worldwide. It is estimated to infect 20-25 million people every year and can a...

Cellular Immune Responses in Typhoid Fever Patients and Vaccinees

Typhoid fever caused by Salmonella Typhi and Paratyphi causes over 21 million cases of febrile illness and 200,000 deaths are attributed to enteric fever each year. Typhoid fever is an ent...

Salmonella Typhi Vi O-Acetyl Pectin-rEPA Conjugate Vaccine

This study will evaluate a new (conjugate) vaccine for typhoid fever, which remains a serious disease especially difficult to treat in developing countries. Salmonella typhi, the bacteria ...

NCCLS Interpretive Criteria for Salmonella

To determine the clinical significance of gene mutations encoding antibiotic resistance, but not expressed as clinical resistance, in Salmonella bacteria

Safety of an Oral HIV Vaccine in HIV Uninfected Volunteers

This study will test the safety of and immune response to an oral HIV vaccine in healthy volunteers. The vaccine in this study uses a weakened bacterium called Salmonella typhi to deliver...

PubMed Articles [2351 Associated PubMed Articles listed on BioPortfolio]

Azithromycin Resistance in Clinical Isolates of Salmonella enterica Serovars Typhi and Paratyphi in Bangladesh.

Salmonella enterica serovars Typhi and Paratyphi, the causative agents of typhoid and paratyphoid, are major threats in developing countries. The present study aimed to investigate the resistance patt...

Characteristics of Resistance Mechanisms and Molecular Epidemiology of Fluoroquinolone-Nonsusceptible Salmonella enterica Serovar Typhi and Paratyphi A Isolates from a Tertiary Hospital in Dhaka, Bangladesh.

The aim of this study was to characterize the fluoroquinolone (FQ) resistance mechanism of Salmonella enterica serovar Typhi and Paratyphi A in Bangladesh. Salmonella Typhi isolates were classified in...

Plasma IgA responses against two Salmonella Typhi antigens identify patients with typhoid fever.

There is a need for a reliable, simple diagnostic assay for typhoid fever. Available commercial serologic assays for typhoid fever have limited sensitivity and specificity. Using high-throughput immun...

OxyR positively and directly regulates Vi polysaccharide capsular antigen in Salmonella enterica serovar Typhi.

Salmonella enterica serovar Typhi (S. Typhi) is a human enteropathogen that can overcome oxidative stress and survive in macrophages. OxyR is an important part of the antioxidant defense system. S. Ty...

A 3' UTR-derived non-coding RNA RibS increases expression of cfa and promotes biofilm formation of Salmonella enterica serovar Typhi.

Bacterial non-coding RNAs (ncRNAs) are widely studied and found to play important roles in regulating various cellular processes. Recently, many ncRNAs have been discovered to be transcribed or proces...

Medical and Biotech [MESH] Definitions

A serotype of SALMONELLA ENTERICA which is the etiologic agent of TYPHOID FEVER.

An acute systemic febrile infection caused by SALMONELLA TYPHI, a serotype of SALMONELLA ENTERICA.

Viruses whose host is Salmonella. A frequently encountered Salmonella phage is BACTERIOPHAGE P22.

A serotype of Salmonella enterica that is a frequent agent of Salmonella gastroenteritis in humans. It also causes PARATYPHOID FEVER.

A serotype of Salmonella enterica which is an etiologic agent of gastroenteritis in man and other animals.

More From BioPortfolio on "Recombinant Attenuated Salmonella Typhi Vaccine Vectors Producing Streptococcus Pneumoniae PspA"

Quick Search


Relevant Topics

Clincial Trials
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...

Food is any substance consumed to provide nutritional support for the body. It is usually of plant or animal origin, and contains essential nutrients, such as carbohydrates, fats, proteins, vitamins, or minerals. The substance is ingested by an organism ...

Pneumonia (bronchopneumonia, lobar pneumonia and double pneumonia) is inflammation (swelling) of the tissue in one or both of your lungs. It is usually caused by an pneumococcal infection caused by bacteria called Streptococcus pneumoniae.  However,...

Searches Linking to this Trial