Safety and Immunogenicity of a Shigella Bivalent Conjugate Vaccine (ZF0901) in 3-Month- to 5-Year-Old Children in China

Yi Mo, Wenjian Fang, Hong Li, Junji Chen, Xiaohua Hu, Bin Wang, Zhengli Feng, Honghua Shi, Ying He, Dong Huang, Zhaojun Mo, Qiang Ye, Lin Du, Yi Mo, Wenjian Fang, Hong Li, Junji Chen, Xiaohua Hu, Bin Wang, Zhengli Feng, Honghua Shi, Ying He, Dong Huang, Zhaojun Mo, Qiang Ye, Lin Du

Abstract

No licensed Shigella vaccine is presently available globally. A double-blinded, randomized, placebo-controlled, age descending phase II clinical trial of a bivalent conjugate vaccine was studied in China. The vaccine ZF0901 consisted of O-specific polysaccharides purified and detoxified from lipopolysaccharide (LPS) of S. flexneri 2a and S. sonnei and covalently bonded to tetanus toxoid. A total of 224, 310, and 434 children, consented by parents or guardians, aged 3 to 6 and 6 to 12 months and 1 to 5 years old, respectively, were injected with half or full doses, with or without adjuvant or control Hib vaccine. There were no serious adverse reactions in all recipients of ZF0901 vaccine independent of age, dosage, number of injections, or the adjuvant status. Thirty days after the last injection, ZF0901 induced robust immune responses with significantly higher levels of type-specific serum antibodies (geometric mean concentrations (GMCs) of IgG anti-LPS) against both serotypes in all age groups compared with the pre-immune or the Hib control (p < 0.0001). Here, we demonstrated that ZF0901 bivalent Shigella conjugate vaccine is safe and immunogenic in infants and young children and is likely suitable for routine immunization.

Keywords: Shigella conjugate vaccine; bivalent; clinical trial; infants and young children; safety and immunogenicity.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Study profile: subject randomization, screening, enrollment, and vaccine assignment of Phase II study of ZF0901 trial. SAE: serious adverse event.
Figure 2
Figure 2
Incidence rate (%) of adverse reactions related to vaccination reported within 30 days after any injections. (A) Combined incidence rate according to ages. Blue bars indicate mild/moderate reactions and orange for grade 3 reactions. There was no statistical significance within the same age group receiving any type or number of vaccine injections or between any age groups (p > 0.5). (B) Comparison of the rate (%) of adverse reactions according to the number of injections and vaccine types. Blue bars indicate fever incidences and orange, for other adverse reactions. There was no statistical significance in the incidence rate between number of injections within the same age group, with or without adjuvant, full, or half dosages (p > 0.1).
Figure 3
Figure 3
Pre-vaccination GMC anti-LPS IgG in all participants. (A). S. flexneri 2a antibody levels at day 0. (B) S. sonnei antibody levels at day 0.
Figure 4
Figure 4
Composite chart of GMC anti-LPS IgG. (A) S. flexneri 2a, (B) S. sonnei.

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