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. 2023 Mar 10;8(1):35.
doi: 10.1038/s41541-023-00624-y.

A Shigella flexneri 2a synthetic glycan-based vaccine induces a long-lasting immune response in adults

Shiri Meron-Sudai #  1 , Valeria Asato #  1 , Amos Adler  1   2 , Anya Bialik  1 , Sophy Goren  1 , Ortal Ariel-Cohen  1 , Arava Reizis  1 , Laurence A Mulard  3 , Armelle Phalipon  4 , Dani Cohen  5
Affiliations

A Shigella flexneri 2a synthetic glycan-based vaccine induces a long-lasting immune response in adults

Shiri Meron-Sudai et al. NPJ Vaccines. .

Abstract

Shigella is a leading cause of moderate to severe diarrhea worldwide and of diarrhea-associated deaths in children under 5 years of age in low-and middle-income countries. A vaccine against shigellosis is in high demand. SF2a-TT15, a synthetic carbohydrate-based conjugate vaccine candidate against Shigella flexneri 2a (SF2a) was found safe and strongly immunogenic in adult volunteers. Here, SF2a-TT15 at 10 µg oligosaccharide (OS) vaccine dose is shown to induce a sustained immune response in magnitude and functionality in the majority of volunteers followed up 2 and 3 years post-vaccination. High levels of either one of the humoral parameters as well as the number of specific-IgG memory B-cells determined 3 months after vaccination were good predictors of the durability of the immune response. This study is the first to examine the long-term durability of antibody functionality and memory B-cell response induced by a Shigella vaccine candidate.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Longevity of serum IgG GMT (95% CI) to SF2a LPS in vaccinees receiving 2 or 10 µg OS doses of non-adjuvanted and adjuvanted SF2a-TT15 and in placebo recipients.
Circles represent individual endpoint titres, green circles represent volunteers receiving the adjuvanted vaccine or placebo. Bars represent the Geometric Mean Titer (GMT) and the 95% Confidence Intervals (CIs) on day 0 (baseline), at 3 months, 2 and 3 years post-last vaccination. *p-value < 0.05; **p-value < 0.01 (vs. day 0).
Fig. 2
Fig. 2. Longevity of SBA GMT (95% CI) in vaccinees receiving 2 or 10 µg OS doses of non-adjuvanted and adjuvanted SF2a-TT15 and in placebo recipients.
Circles represent individual endpoint titers, green circles represent volunteers receiving the adjuvanted vaccine or placebo. Bars represent the geometric mean titres (GMTs) and the 95% Confidence Intervals (CIs) on day 0 (baseline), at 3 months, 2 and 3 years post-vaccination. Serum Bactericidal Activity (SBA): a serum dilution yielding at least 50% reduction in the number of colonies compared with control was defined as having bactericidal activity. The last serum dilution with bactericidal activity was defined as the endpoint titer. *p-value < 0.05; **p-value < 0.01 (vs. day 0).
Fig. 3
Fig. 3. Longevity of Mean Avidity I50 (95% CIs) of IgG serum antibodies to SF2a LPS in vaccinees receiving 2 or 10 µg OS doses of non-adjuvanted and adjuvanted SF2a-TT15 and in placebo recipients.
Circles represent individual I50 index, green circles represent volunteers receiving the adjuvanted vaccine or placebo. Bars represent Mean I50 and the 95% Confidence Intervals (CIs) on day 0 (baseline), at 3 months, 2, and 3 years post-vaccination. **p-value < 0.01 (vs. day 0).
Fig. 4
Fig. 4. Longevity of IgG memory B-cells to SF2a LPS in vaccinees receiving 2 or 10 µg OS doses of non-adjuvanted and adjuvanted SF2a-TT15 and in placebo recipients.
Circles represent individual percent of IgG antibody secreting cells (ASCs) to SF2a LPS /Total IgG ASCs, green circles represent volunteers receiving the adjuvanted vaccine or placebo. Bars represent the Geometric Mean (GM) and 95% Confidence intervals (CIs) of these values on day 0 (baseline), at 3 months, 2 and 3 years post-vaccination. *p-value < 0.05; **p-value < 0.01 (vs. day 0).
Fig. 5
Fig. 5. Upper panel (phase I study), middle panel (at 2-year follow-up) and lower panel (at 3-year follow-up).
Distribution of volunteers in the long-term follow up according to the randomized allocation in the phase I study.
See this image and copyright information in PMC

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