CompletedNCT04056117Updated Jun 23, 2026

A Study to Determine If a New Shigella Vaccine is Safe, Induces Immunity and The Best Dose Among Kenyan Infants

A Phase 1/2 interventional study of Shigella 4V and MenACWY in Shigellosis, sponsored by LimmaTech Biologics AG. Completed at 2 sites in Kenya. Open to participants aged 8 Months to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-06-23.

Sponsored by LimmaTech Biologics AG · Phase 1/2, Interventional, and Prevention

Phase: Phase 1/2
Study type: Interventional
Enrollment: 597
Allocation: Randomized
Ages: 8 Months to 50 Years
Sex: All

Study summary

In this study, the tetravalent bioconjugate candidate vaccine Shigella4V will be tested to obtain first-in-human data on its safety and immunogenicity in infants and to identify the preferred dose of Shigella4V in 9 month old infants.

Read the detailed description

Shigella4V is a tetravalent bioconjugate vaccine including O antigen-polysaccharides of the most predominant Shigella serotypes.

The study will be conducted in two steps. In Step1: safety and reactogenicity of the vaccine will be evaluated first in adults and subsequently in children and infants through an age-descending and dose escalation approach. In Step 2: in order to further evaluate safety and to identify the optimum immunogenic dose, infants will be randomised to receive 1 of 4 different vaccine doses or control vaccine.

Adults will receive a 2 dose schedule, children and infants will receive a 3 dose schedule. For each vaccine dose, formulation with and without Aluminium adjuvant will be tested.

Conditions studied

Shigellosis

Browse trials for

Dysentery, Bacillary 56

In context

Dysentery, Bacillary

56 studies on the registry are indexed under Dysentery, Bacillary; 6 are open to participants now.

This study's enrollment of 597 is above the median of 73 across 48 interventional studies indexed under Dysentery, Bacillary.

Browse Dysentery, Bacillary studies →

Lead sponsor

LimmaTech Biologics AG is the lead sponsor of 10 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 8 Months to 50 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

All ages

Healthy by medical history, laboratory findings and physical examination before entering into the study (Participants with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator)
Seronegative for HIV, hepatitis B and C (as per screening laboratory tests)
Resident in the study area village during the whole trial period (Kilifi -Kilifi Health and Demographic Surveillance System (Described in more detail in the SSA); (Kericho-a 75km radius from the Kericho Clinical Research Centre).
Previously completed routine primary vaccinations (6,10 and 14 weeks or thereabouts) to the best knowledge of the participant/parent/guardian.
Signed/thumb written informed consent, in accordance with local practice, provided by adult volunteers (participants 18 years of age and older), parents or legal representatives for children and infants participants as applicable, who, in the opinion of the investigator, can and will comply with the requirements of the protocol
Demonstrated comprehension of the protocol procedures by passing score of 90% or better on a written/verbal comprehension test.

Adults

Female and male participants between, and including 18-50 years at the time of first vaccination
Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause. Female volunteers of childbearing potential may be enrolled in the study if the participant: has a negative urine pregnancy test at the day of screening and vaccinations, respectively, and
- agree to use effective contraception for 30 days prior to vaccination and
- agree to continue contraception at least for 2 months after completion of vaccination series.

Children and Infants

Female and male aged 9 months (+/- 1 month) old (infants) or between, and including, 2-5 years of age (children) at the time of the first vaccination
Born full-term (i.e. after a gestation period of 37 to less than 42 completed weeks)

Exclusion criteria

Exclusion Criteria:

All ages

Any clinically significant deviation from the normal range in biochemistry or haematological blood tests.
Suspected or known hypersensitivity (including allergy) to any of the vaccine components or to previous vaccine, or to medicinal products or medical equipment whose use is foreseen in this study
Clinical conditions representing a contraindication to intramuscular vaccination and blood draws
Any confirmed or suspected immunosuppressive or immune-deficient condition.
Systemic administration of corticosteroids (PO/IV/IM): prednisone ≥20 mg/day, or equivalent for more than 14 consecutive days from birth (for infants) / within 90 days prior to informed consent. Inhaled except for doses > 800 mg/day and topical steroids are allowed.
Administration of antineoplastic or radiotherapy from birth / within 90 days prior to informed consent. Participants may be on chronic or as needed medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to participant safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening of medical diagnosis or condition
Known exposure to Shigella during lifetime of the subject
Concurrently participating in another clinical study, or participation in the preceding month, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device)
Acute disease and /or fever at the time of enrolment Note: enrolment may be postponed/delayed until such transient circumstances have terminated
History of any malignancy of lymphoproliferative disorder
Known to be part of study personnel or being a close family member to the personnel conducting this study.
Previous history of significant persistent neutropenia, or drug related Neutropenia
Adults with clinical wasting; children with weight-for-age Z score less than -3SD.
History of any chronic or progressive disease (e.g., neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease) that according to judgment of the investigator could interfere with the study outcomes or pose a threat to the participant's health
History of surgical splenectomy or Sickle cell disease (SCD test performed at KEMRI-CGMRC only).
Administration of immunoglobulin and/or any blood products within the three months preceding the first dose of study vaccine
Any medical, social condition, or occupational reason that, in the judgment of the investigator, is a contraindication to protocol participation or impairs the volunteer's/parent's/guardian's ability to give informed consent, increases the risk to the potential participant because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data .

Adults

Women who are breastfeeding
History of chronic alcohol consumption and/or drug abuse. Chronic alcohol consumption is defined as: a prolonged period of frequent, heavy alcohol use; the inability to control drinking once it has begun; physical dependence manifested by withdrawal symptoms when the individual stops using alcohol; tolerance, or the need to use more and more alcohol to achieve the same effects; a variety of social and/or legal problems arising from alcohol use.

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 597 participants (actual)

Study arms

Experimental
NA (Non-adjuvanted) - very low dose - infants
Infants receive 3 very low doses of the non-adjuvanted investigational product
Biological: Shigella 4V
Experimental
A (adjuvanted) - very low dose - infants
Infants receive 3 very low doses of the adjuvanted investigational product
Biological: Shigella 4V
Experimental
NA (Non-adjuvanted) - low dose -infants
Infants receive 3 low doses of the non-adjuvanted investigational product
Biological: Shigella 4V
Experimental
A (adjuvanted) - low dose - infants
Infants receive 3 low doses of the adjuvanted investigational product
Biological: Shigella 4V
Experimental
NA (non-adjuvanted) - medium dose - infants
Infants receive 3 medium doses of the non-adjuvanted investigational product
Biological: Shigella 4V
Experimental
A (adjuvanted) - medium dose - infants
Infants receive 3 medium doses of the adjuvanted investigational product
Biological: Shigella 4V
Experimental
NA (non-adjuvanted) - medium dose - children
Children receive 3 medium doses of the non-adjuvanted investigational product
Biological: Shigella 4V
Experimental
A (adjuvanted) - medium dose - children
Children receive 3 medium doses of the adjuvanted investigational product
Biological: Shigella 4V
Experimental
NA (non-adjuvanted) - medium dose-adults
Adults receive 2 medium doses of the non-adjuvanted investigational product
Biological: Shigella 4V
Experimental
A (adjuvanted) - medium dose - adults
Adults receive 2 medium doses of the adjuvanted investigational product
Biological: Shigella 4V
Experimental
NA (non-adjuvanted) - high dose - infants
Infants receive 3 high doses of the non-adjuvanted investigational product
Biological: Shigella 4V
Experimental
A (adjuvanted) - high dose - infants
Infants receive 3 high doses of the adjuvanted investigational product
Biological: Shigella 4V
Experimental
NA (non-adjuvanted) - high dose - children
Chilldren receive 3 high doses of the non-adjuvanted investigational product
Biological: Shigella 4V
Experimental
A (adjuvanted) - high dose - children
Chilldren receive 3 high doses of the adjuvanted investigational product
Biological: Shigella 4V
Experimental
NA (non-adjuvanted) - high dose - adults
Adults receive 2 high doses of the non-adjuvanted investigational product
Biological: Shigella 4V
Experimental
A (adjuvanted) - high dose - adults
Adults receive 2 high doses of the adjuvanted investigational product
Biological: Shigella 4V
Experimental
MenACWY-Placebo
Adults receive one administration of MenACWY followed by one placebo administration
Biological: MenACWY · Biological: Placebo
Other
Rabies
Children receive three administrations of Rabies
Biological: Rabies
Other
MenACWY-DTaP
Infants receive two administrations of MenACWY followed by DTaP administration
Biological: MenACWY · Biological: Diphtheria, Tetanus and Pertussis (DTaP)

Interventions

BiologicalShigella 4V
Non-adjuvanted and adjuvanted Shigella 4V administrated at 4 different doses: very low, low, medium and high.
BiologicalMenACWY
Control vaccine administrated to adults and infants
BiologicalRabies
Control vaccine administrated to children
BiologicalDiphtheria, Tetanus and Pertussis (DTaP)
Control vaccine administrated to infants
BiologicalPlacebo
Control administrated to adults

What researchers measure

Primary outcomes

Safety - Solicited Local and Systemic Adverse Events (AEs)
Safety and tolerability of the candidate vaccine Shigella4V as determined by occurrence, severity and relationship of solicited AEs
Time frame: during 7 days following each vaccination
Safety - Unsolicited Adverse Events (AEs)
Safety and tolerability of the candidate vaccine Shigella4V as determined by occurrence, severity and relationship of unsolicited AEs
Time frame: during 28 days following each vaccination
Safety - Serious Adverse Events (SAEs)
Safety and tolerability of the candidate vaccine Shigella4V as determined by occurrence, severity and relationship of SAEs
Time frame: throughout the study duration, up to 15 months
Immunology - change in serum immunoglobulin G (IgG)
Serum IgG responses and fold-increases between post- and pre-vaccination samples from infants of step 2, as determined by enzyme-linked immunosorbent assay (ELISA) against lipopolysaccharide (LPS) corresponding to the 4 Shigella serotypes included in the Shigella4V bioconjugate.
Time frame: throughout the study, up to 15 months

Secondary outcomes

Safety - clinically significant changes in cell blood count (CBC) with differentials
Assess the safety of the candidate vaccine Shigella4V by measuring clinical significant changes in haematological safety parameters
Time frame: throughout the study, up to 15 months
Safety - clinically significant changes in creatinine level
Assess the safety of the candidate vaccine Shigella4V by measuring clinical significant changes in biochemical safety parameters
Time frame: throughout the study, up to 15 months
Safety - clinically significant changes in alanine aminotransferase (ALT) level
Assess the safety of the candidate vaccine Shigella4V by measuring clinical significant changes in biochemical safety parameters
Time frame: throughout the study, up to 15 months
Safety - clinically significant changes in aspartate aminotransferase (AST) level
Assess the safety of the candidate vaccine Shigella4V by measuring clinical significant changes in biochemical safety parameters
Time frame: throughout the study, up to 15 months
Immunogenicity - change is serum IgG
Serum IgG responses and fold-increases between post- and pre-vaccination samples from all participants of step 1, as determined by ELISA against LPS corresponding to the 4 Shigella serotypes included in the Shigella4V bioconjugate.
Time frame: throughout the study, up to 15 months
Immunogenicity - change in anti-Shigella LPS antibody titre
Percentage of participants (from step 1 and 2) achieving at least a four-fold rise in anti-Shigella LPS antibody titre after each injection compared to baseline.
Time frame: throughout the study, up to 15 months

Study locations

2 sites

Kenya Medical Research Institute (KEMRI)/ United States Army Medical Research Directorate- Kenya (USAMRD-K)
Kericho, 1357-20200, Kenya
KEMRI-Centre Geographic Medical Research-COAST (KEMRI-CGMRC)
Kilifi, 230-80108, Kenya

References and documents

Publications

GBD 2015 LRI Collaborators. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory tract infections in 195 countries: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Infect Dis. 2017 Nov;17(11):1133-1161. doi: 10.1016/S1473-3099(17)30396-1. Epub 2017 Aug 23. PubMed 28843578 ↗
Livio S, Strockbine NA, Panchalingam S, Tennant SM, Barry EM, Marohn ME, Antonio M, Hossain A, Mandomando I, Ochieng JB, Oundo JO, Qureshi S, Ramamurthy T, Tamboura B, Adegbola RA, Hossain MJ, Saha D, Sen S, Faruque AS, Alonso PL, Breiman RF, Zaidi AK, Sur D, Sow SO, Berkeley LY, O'Reilly CE, Mintz ED, Biswas K, Cohen D, Farag TH, Nasrin D, Wu Y, Blackwelder WC, Kotloff KL, Nataro JP, Levine MM. Shigella isolates from the global enteric multicenter study inform vaccine development. Clin Infect Dis. 2014 Oct;59(7):933-41. doi: 10.1093/cid/ciu468. Epub 2014 Jun 23. PubMed 24958238 ↗
Mani S, Wierzba T, Walker RI. Status of vaccine research and development for Shigella. Vaccine. 2016 Jun 3;34(26):2887-2894. doi: 10.1016/j.vaccine.2016.02.075. Epub 2016 Mar 12. PubMed 26979135 ↗
Ashkenazi S, Cohen D. An update on vaccines against Shigella. Ther Adv Vaccines. 2013 Sep;1(3):113-23. doi: 10.1177/2051013613500428. PubMed 24757519 ↗
Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, Wu Y, Sow SO, Sur D, Breiman RF, Faruque AS, Zaidi AK, Saha D, Alonso PL, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ochieng JB, Omore R, Oundo JO, Hossain A, Das SK, Ahmed S, Qureshi S, Quadri F, Adegbola RA, Antonio M, Hossain MJ, Akinsola A, Mandomando I, Nhampossa T, Acacio S, Biswas K, O'Reilly CE, Mintz ED, Berkeley LY, Muhsen K, Sommerfelt H, Robins-Browne RM, Levine MM. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet. 2013 Jul 20;382(9888):209-22. doi: 10.1016/S0140-6736(13)60844-2. Epub 2013 May 14. PubMed 23680352 ↗
Anderson M, Sansonetti PJ, Marteyn BS. Shigella Diversity and Changing Landscape: Insights for the Twenty-First Century. Front Cell Infect Microbiol. 2016 Apr 19;6:45. doi: 10.3389/fcimb.2016.00045. eCollection 2016. PubMed 27148494 ↗
Kotloff KL, Platts-Mills JA, Nasrin D, Roose A, Blackwelder WC, Levine MM. Global burden of diarrheal diseases among children in developing countries: Incidence, etiology, and insights from new molecular diagnostic techniques. Vaccine. 2017 Dec 14;35(49 Pt A):6783-6789. doi: 10.1016/j.vaccine.2017.07.036. Epub 2017 Jul 29. PubMed 28765005 ↗
Juergens C, de Villiers PJ, Moodley K, Jayawardene D, Jansen KU, Scott DA, Emini EA, Gruber WC, Schmoele-Thoma B. Safety and immunogenicity of 13-valent pneumococcal conjugate vaccine formulations with and without aluminum phosphate and comparison of the formulation of choice with 23-valent pneumococcal polysaccharide vaccine in elderly adults: a randomized open-label trial. Hum Vaccin Immunother. 2014;10(5):1343-53. doi: 10.4161/hv.27998. Epub 2014 Feb 27. PubMed 24576885 ↗
Bryant K, McVernon J, Marchant C, Nolan T, Marshall G, Richmond P, Marshall H, Nissen M, Lambert S, Aris E, Mesaros N, Miller J. Immunogenicity and safety of measles-mumps-rubella and varicella vaccines coadministered with a fourth dose of Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine in toddlers: a pooled analysis of randomized trials. Hum Vaccin Immunother. 2012 Aug;8(8):1036-41. doi: 10.4161/hv.20357. Epub 2012 Aug 1. PubMed 22617844 ↗
Miller E, Andrews N, Waight P, Findlow H, Ashton L, England A, Stanford E, Matheson M, Southern J, Sheasby E, Goldblatt D, Borrow R. Safety and immunogenicity of coadministering a combined meningococcal serogroup C and Haemophilus influenzae type b conjugate vaccine with 7-valent pneumococcal conjugate vaccine and measles, mumps, and rubella vaccine at 12 months of age. Clin Vaccine Immunol. 2011 Mar;18(3):367-72. doi: 10.1128/CVI.00516-10. Epub 2010 Dec 29. PubMed 21191076 ↗
Taylor DN, Trofa AC, Sadoff J, Chu C, Bryla D, Shiloach J, Cohen D, Ashkenazi S, Lerman Y, Egan W, et al. Synthesis, characterization, and clinical evaluation of conjugate vaccines composed of the O-specific polysaccharides of Shigella dysenteriae type 1, Shigella flexneri type 2a, and Shigella sonnei (Plesiomonas shigelloides) bound to bacterial toxoids. Infect Immun. 1993 Sep;61(9):3678-87. doi: 10.1128/iai.61.9.3678-3687.1993. PubMed 8359890 ↗
Ashkenazi S, Passwell JH, Harlev E, Miron D, Dagan R, Farzan N, Ramon R, Majadly F, Bryla DA, Karpas AB, Robbins JB, Schneerson R. Safety and immunogenicity of Shigella sonnei and Shigella flexneri 2a O-specific polysaccharide conjugates in children. J Infect Dis. 1999 Jun;179(6):1565-8. doi: 10.1086/314759. PubMed 10228084 ↗

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 23, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT04056117
Lead sponsor: LimmaTech Biologics AG
Collaborators: Kenya Medical Research Institute, KEMRI-Wellcome Trust Collaborative Research Program
Responsible party: Sponsor
First posted: Aug 14, 2019
Start date: Sep 2, 2019
Primary completion: Sep 1, 2022
Completion: Nov 14, 2022
Last update: Jun 23, 2026

Study contacts

Mainga Hamaluba, MD

principal investigator · KEMRI/Welcome Trust Research Programme,Kilifi, Kenya

Josphat Kosgei, MD

principal investigator · Medical Research Institute, Kericho, Kenya

Oversight

Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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