Safety and immunogenicity of the synthetic carbohydrate conjugate vaccine, SF2a-TT15, against Shigella flexneri 2a in infants in Kenya: a phase 2a, age-descending, dose-escalating, double-blind, randomised, placebo-controlled study.

Authors

Frederic Sawe, Lucy Koech, Souhir Neffati, Beatrice Korir, Renee M Laird, Elizabeth Odundo, Mary Kirui, Kristen A Clarkson, Cécile Artaud, Mohand Ait-Ahmed, Robert W Kaminski, Akamol E Suvarnapunya, Dani Cohen, Laurence A Mulard, Christiane Gerke, Armelle Phalipon

Published in

The Lancet. Infectious diseases. Aug 19, 2026. Epub Aug 19, 2026.

Abstract

Shigella is the leading cause of morbidity and mortality in children younger than 5 years in low- and middle-income countries and is a major actor in antimicrobial resistance. An effective vaccine is urgently needed. SF2a-TT15, a conjugate featuring a synthetic 15-mer oligosaccharide surrogate of the O-antigen component of Shigella flexneri 2a (SF2a) lipopolysaccharide, was previously shown to be safe and immunogenic in a first-in-human study. We aimed to assess its safety and immunogenicity in infants from an endemic setting, the target population for a Shigella vaccine.
We conducted a phase 2a, age-descending, dose-escalating, double-blind, randomised, placebo-controlled study at the Clinical Research Center, Kenya Medical Research Institute/Walter Reed Army Institute of Research (Kericho, Kenya). Healthy adults aged 18-50 years and healthy children aged 2-5 years with a weight-for-age Z score of -2 or more were randomly assigned (3:1) to receive a 10 μg oligosaccharide dose of SF2a-TT15 adjuvanted with aluminium hydroxide (alum) or matching placebo. Healthy infants aged 9 months plus or minus 1 month with a weight-for-age Z score of -2 or more were randomly assigned (3:3:3:3:1:1) in a stepwise manner to receive a 2 μg oligosaccharide dose of non-alum-adjuvanted SF2a-TT15, a 2 μg oligosaccharide dose of alum-adjuvanted SF2a-TT15, a 10 μg oligosaccharide dose of non-alum-adjuvanted SF2a-TT15, a 10 μg oligosaccharide dose of alum-adjuvanted SF2a-TT15, non-alum-adjuvanted placebo, or alum-adjuvanted placebo, concomitantly with routine measles-rubella vaccination. Study products were administered intramuscularly on day 0, 90, and 270, with a 6-month follow-up after the last injection. The randomisation sequence was computer-generated and randomisation was stratified by cohort and treatment group. Syringes were over-labelled before injection to maintain masking; all clinical site teams were masked except the pharmacist team, including the pharmacy data quality monitoring team, and one person in the Institut Pasteur team. All participants were also masked. Progression between cohorts and dose levels was overseen by an independent data monitoring committee. The primary outcomes were the incidence of adverse events in all cohorts and immunogenicity in the infant cohort, as measured at days 14 and 28 after each injection and at the end of the study by serum IgG antibodies to SF2a lipopolysaccharide and proportion of responders. Safety endpoints were analysed in all participants receiving at least one injection and immunogenicity endpoints were analysed in the full analysis set and in the per-protocol analysis set. This study is registered with ClinicalTrials.gov, NCT04602975, and is completed.
Enrolment was between Oct 26, 2020, and Jan 5, 2022. 54 adults were screened for eligibility, 16 of whom were enrolled and randomly assigned to the adjuvanted 10 μg oligosaccharide dose (n=12) or adjuvanted placebo (n=4). 30 children were screened for eligibility, 16 of whom were enrolled and randomly assigned to the adjuvanted 10 μg oligosaccharide dose (n=12) or adjuvanted placebo (n=4). 413 infants were screened for eligibility, 216 of whom were enrolled and randomly assigned to the non-adjuvanted 2 μg oligosaccharide dose (n=46), the adjuvanted 2 μg oligosaccharide dose (n=44), the non-adjuvanted 10 μg oligosaccharide dose (n=41), the adjuvanted 10 μg oligosaccharide dose (n=43), non-adjuvanted placebo (n=22), or adjuvanted placebo (n=20). 112 (52%) of 215 infants in the safety analysis set were female and 103 (48%) were male. The SF2a-TT15 glycoconjugate was well tolerated and induced high serum IgG geometric mean titres (GMTs) to SF2a lipopolysaccharide in adults and children. In infants, SF2a-TT15 was well tolerated at both doses, adjuvanted or non-adjuvanted, with no vaccine-related serious adverse events. 202 (94%) of 216 infants had at least one unsolicited adverse event. 182 (90%) of these infants had adverse events considered not related to study products. No significant differences in the frequency of unsolicited adverse events were reported between any treatment groups (p>0·05 for all comparisons). 1235 adverse events were recorded in the infant cohort, most being unrelated to the study product (1226 [99%]) and of mild (744 [60%]) or moderate (435 [35%]) grading. At 28 days after each injection and for both doses, adjuvanted or non-adjuvanted, SF2a-TT15 induced significantly higher serum IgG GMTs to SF2a lipopolysaccharide compared with corresponding GMTs in placebo recipients (p=0·047 for the non-adjuvanted 2 μg oligosaccharide dose 28 days after the first injection and p<0·001 for all the other comparisons). The highest GMTs were elicited in the adjuvanted 10 μg oligosaccharide dose group (11 240·0 [95% CI 6187·6-20 418·0]), corresponding to a geometric mean ratio (GMR) of 55·0 (95% CI 30·3-99·7) with 93·8% (95% CI 79·2-99·2) of responders at 14 days after the first injection, and increased to 28 528·3 (18 805·1-43 279·0), corresponding to a GMR of 139·6 (79·5-245·2) with 100% (89·1-100·0) of responders at 14 days after the second injection, with no further increase after the boost vaccine. The adjuvanted 2 μg oligosaccharide dose group had significantly higher serum IgG GMTs to SF2a lipopolysaccharide than the non-adjuvanted 2 μg oligosaccharide dose group (p<0·001 at day 28 after the two first injections, p=0·022 at 28 days after the boost vaccine), but GMT were not significantly different between the adjuvanted and non-adjuvanted 10 μg oligosaccharide dose SF2a-TT15 groups (p>0·5 for all timepoints). At the end of the study, for both doses, adjuvanted or not, GMTs were decreased but were still significantly elevated compared with the placebo group (p<0·001).
SF2a-TT15 is well tolerated and strongly immunogenic in Kenyan infants, showing potential for further development. Available data support advancing a multivalent synthetic glycan-based Shigella vaccine.
Gates Foundation, The Wellcome Trust, The European Union Seventh Framework Programme, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases, and Institut Pasteur.
For the Kiswahili translation of the abstract see Supplementary Materials section.

PMID:
42617627
Bibliographic data and abstract were imported from PubMed on 20 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.