Shigella Sonnel O-SPC/rBRU Conjugate Vaccine

NCT01369927 | Completed Phase 1

• 2 other identifiers: 99991113811-CH-N138
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The active ingredient of this Shigella sonnei O-SP-core conjugate vaccine is a saccharide-protein conjugate composed of a fragment of S. sonnei LPS. The saccharide component consists of an average of 3.5 repeat units of the O-SP plus the core region of the LPS (O-SPC). The O-SPC is covalently bound to the recombinant non-toxic exoprotein B of Clostridium difficile. The objective of this phase of the study is to determine if this vaccine is safe and can induce IgG antibody type-specific immunity to shigellosis in adults. The overall objective is to determine if this vaccine can elicit higher levels of IgG antibody than the previous experimental vaccines made with the full length O-SP, shown to be \>70% efficacious in greater than or equal to3 year old children, to induce type-specific immunity to shigellosis in younger children. Sixty 18-49 years-old healthy adults will be recruited in Israel. Volunteers will be vaccinated on a random basis with one i.m. injection of 10 or 25 micrograms of the investigational conjugate vaccine. Local and systemic reactions will be observed at 30 minutes, and the volunteers will be instructed to take their temperature and examine the injection site for redness and swelling and fill out a questionnaire at 6, hours and daily for 7 days after vaccination. The volunteers will visit the clinic at 24 or 48 hours following the injection and any time they request it. The study will commence with 5 volunteers injected with the 10ug dose to be followed, if no severe adverse reactions occur, by 5 volunteers injected with the 25ug dose. If a severe adverse reaction occurs on 1 of the 5 volunteers in either group, 5 more will be injected with that dose. If there are no severe adverse reactions the study will proceed. If there is one more severe reaction the study will be halted and re-evaluated by the IRB and the FDA. Vaccine-induced antibodies will be measured at 1 and 6 months after immunization, and compared to those elicited by our previous S. sonnei conjugate vaccines. There is a body of evidence that a critical level of serum IgG antibody to the O-specific polysaccharide domain of LPS confers type-specific immunity to S. sonnei as well as to other Shigella:

1. 1.Shigellosis is rarely observed in infants up to the age of 4-6 months. The most obvious explanation for this is that maternally-derived serum IgG provides this immunity;
2. 2.There is an age-related development of IgG anti-LPS antibodies that, in many instances, is not induced by the homologous bacteria but by non-pathogenic cross-reacting enteric bacteria;
3. 3.The highest incidence, morbidity, and mortality occur during 6 months to 6 years of age when the maternally-derived serum anti-O-SP has waned and the naturally-derived antibodies have not yet appeared;
4. 4.One injection of a S. sonnei-rEPA conjugate showed significant protection against shigellosis in Israeli Defense Force soldiers. Vaccinees who developed shigellosis showed significantly lower serum IgG responses to the homologous LPS than those did not.The high antibody level induced by the conjugate vaccine indicates the positive correlation between the serum IgG anti-LPS levels and immunity to S. sonnei infection;
5. 5.Following Phase 1 and Phase 2 studies that showed safety and age-related immunogenicity, a double-blinded randomized and vaccine-controlled Phase 3 evaluation of S. sonnei and S. flexneri type 2a O-specific polysaccharide (O-SP) protein conjugates was conducted among 1-4 year-olds in Israel.

Conditions

Immunogenicity; Shigellosis

Keywords

Shigellosis; Safety and Immunogenicity; Conjugate Vaccine

Outcome Measures

Primary Outcomes (1)

• Vaccine safety

Secondary Outcomes (2)

• Induction of IgG antibody type-specific immunity to shigellosis in adults.

• Tertiary: Induction of higher levels of IgG antibody than the previous experimental vaccines made with full length O-SP for type specific immunity to shigellosis in younger children.

Interventions

Shigella Sonnei O-SPC/rBRU BIOLOGICAL

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• Healthy adults, 18 to 49 years of age of either sex who do not have any of the following conditions will be eligible to participate:
• A chronic or progressive disease requiring chronic medication,
• History of splenectomy or abnormal immune system,
• History of neurological symptoms or signs, or mental illness,
• Anaphylactic shock following administration of any vaccine or any other severe allergic reaction,
• Women who are pregnant or intend to become pregnant during the vaccine study,
• Had S. sonnei shigellosis in the past year or received a S. sonnei vaccine previously,
• Have received systemic steroids during the month preceding Shigella vaccination,
• Had cancer, HIV/AIDS, Hepatitis B or C, Guillain Barre Syndrome, chronic skin disease or have abnormal liver functions or blood counts.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead

Study Sites (1)

Schneider Children's Hospital

Petah Tikva, Israel

Location

Related Publications (3)

• Dagan R, Eskola J, Leclerc C, Leroy O. Reduced response to multiple vaccines sharing common protein epitopes that are administered simultaneously to infants. Infect Immun. 1998 May;66(5):2093-8. doi: 10.1128/IAI.66.5.2093-2098.1998.

  PMID: 9573094 BACKGROUND

• Passwell JH, Ashkenazi S, Banet-Levi Y, Ramon-Saraf R, Farzam N, Lerner-Geva L, Even-Nir H, Yerushalmi B, Chu C, Shiloach J, Robbins JB, Schneerson R; Israeli Shigella Study Group. Age-related efficacy of Shigella O-specific polysaccharide conjugates in 1-4-year-old Israeli children. Vaccine. 2010 Mar 2;28(10):2231-2235. doi: 10.1016/j.vaccine.2009.12.050. Epub 2010 Jan 5.

  PMID: 20056180 BACKGROUND

• Zilberberg MD. Assessment of reporting bias for Clostridium difficile hospitalizations, United States. Emerg Infect Dis. 2008 Aug;14(8):1334. doi: 10.3201/eid1408.080446. No abstract available.

  PMID: 18680680 BACKGROUND

MeSH Terms

Conditions

Dysentery, Bacillary

Condition Hierarchy (Ancestors)

Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Dysentery; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Feng-Ying C Lin, M.D.

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 8, 2011
• First Posted: June 9, 2011
• Study Start: May 15, 2011
• Primary Completion: April 24, 2013
• Study Completion: April 24, 2013
• Last Updated: December 16, 2019

Record last verified: 2013-04-24

Locations

IL (1)