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

doi:10.3390/vaccines10010033

. 2021 Dec 28;10(1):33.

doi: 10.3390/vaccines10010033.

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

Yi Mo¹, Wenjian Fang², Hong Li³, Junji Chen¹, Xiaohua Hu², Bin Wang³, Zhengli Feng¹, Honghua Shi⁴, Ying He⁴, Dong Huang⁵, Zhaojun Mo¹, Qiang Ye³, Lin Du^{2

6}

Affiliations

¹ Guangxi Center for Disease Prevention and Control, Nanning 530027, China.
² Beijing Zhifei Lvzhu Biopharmaceutical Co., Ltd., Beijing 100176, China.
³ National Institutes for Food and Drug Control, Beijing 102629, China.
⁴ Yongfu Center for Disease Prevention and Control, Guilin 541800, China.
⁵ Yizhou Center for Disease Prevention and Control, Hechi 546399, China.
⁶ Beijing Bacterial Vaccine Engineering Research Centre, Beijing 100176, China.

PMID: 35062694
PMCID: PMC8780113
DOI: 10.3390/vaccines10010033

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

Yi Mo et al. Vaccines (Basel). 2021.

. 2021 Dec 28;10(1):33.

doi: 10.3390/vaccines10010033.

Authors

Yi Mo¹, Wenjian Fang², Hong Li³, Junji Chen¹, Xiaohua Hu², Bin Wang³, Zhengli Feng¹, Honghua Shi⁴, Ying He⁴, Dong Huang⁵, Zhaojun Mo¹, Qiang Ye³, Lin Du^{2

6}

Affiliations

¹ Guangxi Center for Disease Prevention and Control, Nanning 530027, China.
² Beijing Zhifei Lvzhu Biopharmaceutical Co., Ltd., Beijing 100176, China.
³ National Institutes for Food and Drug Control, Beijing 102629, China.
⁴ Yongfu Center for Disease Prevention and Control, Guilin 541800, China.
⁵ Yizhou Center for Disease Prevention and Control, Hechi 546399, China.
⁶ Beijing Bacterial Vaccine Engineering Research Centre, Beijing 100176, China.

PMID: 35062694
PMCID: PMC8780113
DOI: 10.3390/vaccines10010033

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Study profile: subject randomization, screening, enrollment, and vaccine assignment of Phase II study of ZF0901 trial. SAE: serious adverse event.

**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**
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**
Composite chart of GMC anti-LPS IgG. (A) *S. flexneri* 2a, (B) *S. sonnei*.

See this image and copyright information in PMC

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[1] Kotloff K.L., Riddle M.S., Platts-Mills J.A., Pavlinac P., Zaidi A.K.M. Shigellosis. Lancet. 2018;391:801–812. doi: 10.1016/S0140-6736(17)33296-8. - DOI - PubMed

[2] Kotloff K.L., Riddle M.S., Platts-Mills J.A., Pavlinac P., Zaidi A.K.M. Shigellosis. Lancet. 2018;391:801–812. doi: 10.1016/S0140-6736(17)33296-8. - DOI - PubMed

[3] Baker S., The H.C. Recent insights into Shigella. Curr. Opin. Infect. Dis. 2018;31:449–454. doi: 10.1097/QCO.0000000000000475. - DOI - PMC - PubMed

[4] Baker S., The H.C. Recent insights into Shigella. Curr. Opin. Infect. Dis. 2018;31:449–454. doi: 10.1097/QCO.0000000000000475. - DOI - PMC - PubMed

[5] Zachariah O.H., Lizzy M.A., Rose K., Angela M.M. Multiple drug resistance of Campylobacter jejuni and Shigella isolated from diarrhoeic children at Kapsabet County referral hospital, Kenya. BMC Infect. Dis. 2021;21:109. doi: 10.1186/s12879-021-05788-3. - DOI - PMC - PubMed

[6] Zachariah O.H., Lizzy M.A., Rose K., Angela M.M. Multiple drug resistance of Campylobacter jejuni and Shigella isolated from diarrhoeic children at Kapsabet County referral hospital, Kenya. BMC Infect. Dis. 2021;21:109. doi: 10.1186/s12879-021-05788-3. - DOI - PMC - PubMed

[7] Rizi K.S., Farsiani H., Sasan M.S. High rate of resistance to ceftriaxone and azithromycin among Shigella spp. isolates at three children’s referral hospitals in Northeast Iran. J. Infect. Chemother. 2020;26:955–958. doi: 10.1016/j.jiac.2020.04.022. - DOI - PubMed

[8] Rizi K.S., Farsiani H., Sasan M.S. High rate of resistance to ceftriaxone and azithromycin among Shigella spp. isolates at three children’s referral hospitals in Northeast Iran. J. Infect. Chemother. 2020;26:955–958. doi: 10.1016/j.jiac.2020.04.022. - DOI - PubMed

[9] Khalil I.A., Troeger C., Blacker B.F., Rao P.C., Brown A., Atherly D.E., Brewer T.G., Engmann C.M., Houpt E.R., Kang G., et al. Morbidity and mortality due to Shigella and Enterotoxigenic Escherichia coli diarrhoea: The Global Burden of Disease Study 1990–2016. Lancet Infect. Dis. 2018;18:1229–1240. doi: 10.1016/S1473-3099(18)30475-4. - DOI - PMC - PubMed

[10] Khalil I.A., Troeger C., Blacker B.F., Rao P.C., Brown A., Atherly D.E., Brewer T.G., Engmann C.M., Houpt E.R., Kang G., et al. Morbidity and mortality due to Shigella and Enterotoxigenic Escherichia coli diarrhoea: The Global Burden of Disease Study 1990–2016. Lancet Infect. Dis. 2018;18:1229–1240. doi: 10.1016/S1473-3099(18)30475-4. - DOI - PMC - PubMed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

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