Safety and immunogenicity of Shigella sonnei-CRM9 and Shigella flexneri type 2a-rEPAsucc conjugate vaccines in one- to four-year-old children

Justen H. Passwell; Shai Ashkenazi; Efrat Harlev; Dan Miron; Reut Ramon; Nahid Farzam; Liat Lerner-geva; Yonit Levi; Chiayung Chu; Joseph Shiloach; John B. Robbins; Rachel Schneerson

doi:10.1097/01.inf.0000078156.03697.a5

Safety and immunogenicity of Shigella sonnei-CRM₉ and Shigella flexneri type 2a-rEPA_succ conjugate vaccines in one- to four-year-old children

Justen H. Passwell, Shai Ashkenazi, Efrat Harlev, Dan Miron, Reut Ramon, Nahid Farzam, Liat Lerner-geva, Yonit Levi, Chiayung Chu, Joseph Shiloach, John B. Robbins, Rachel Schneerson

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Abstract

Background and objective. Shigella conjugate vaccines have been shown to be safe, immunogenic and efficacious in adult volunteers. We have now investigated the safety and immunogenicity of investigational Shigella sonnei and Shigella flexneri 2a conjugate vaccines in 1- to 4-year-old children, the age group at greatest risk for shigellosis. Methods. The O-specific polysaccharides of S. sonnei and S. flexneri 2a, the two most common shigellae from patients in Israel, were bound to medically useful carrier proteins to form conjugates. Eighty healthy 1- to 4-year-olds were randomized to receive two 0.5-ml im injections 6 weeks apart of either S. sonnei-CRM₉ or S. flexneri 2a-rEPA_succ. Blood was taken before, 6 weeks after the first injection, 4 weeks after the second injections and 2 years after immunization for assay of IgG anti-lipopolysaccharide, diphtheria toxin and Pseudomonas aeruginosa exotoxin A antibodies by enzyme-linked immunosorbent assay. Results. During an 8-day surveillance period after each immunization, low fever (37.8-39.0°C) lasting only 24 to 48 h occurred in 2 of 40 recipients after the first injection and 4 of 40 recipients after the second injection of S. flexneri 2arEPA_succ and in 2 of 38 of S. sonnei-CRM₉ after the second injection; no fever was detected after the first injection. Liver function tests were normal in all vaccinees. S. sonnei-CRM9 elicited a >4-fold rise in IgG anti-LPS in 92.1% and S. flexneri 2a-rEPA_succ in 85% (P < 0.0001) after the second injection; both conjugates elicited type-specific booster responses. At 2 years the geometric mean concentrations of both IgG anti-lipopolysaccharides were significantly higher than preimmunization levels. A >4-fold rise of IgG anti-diphtheria (65.8%) and IgG anti-ETA (77.5%) was observed. Conclusion. These experimental Shigella conjugate vaccines were safe and immunogenic in 1 to 4-year-old children.

Original language	English
Pages (from-to)	701-706
Number of pages	6
Journal	Pediatric Infectious Disease Journal
Volume	22
Issue number	8
DOIs	https://doi.org/10.1097/01.inf.0000078156.03697.a5
State	Published - 1 Aug 2003
Externally published	Yes

Keywords

Conjugate vaccines
Immunization
Shigellosis

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10.1097/01.inf.0000078156.03697.a5

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Passwell, J. H., Ashkenazi, S., Harlev, E., Miron, D., Ramon, R., Farzam, N., Lerner-geva, L., Levi, Y., Chu, C., Shiloach, J., Robbins, J. B., & Schneerson, R. (2003). Safety and immunogenicity of Shigella sonnei-CRM₉ and Shigella flexneri type 2a-rEPA_succ conjugate vaccines in one- to four-year-old children. Pediatric Infectious Disease Journal, 22(8), 701-706. https://doi.org/10.1097/01.inf.0000078156.03697.a5

@article{ba097d8161ce4087ab3af9bb5038a449,

title = "Safety and immunogenicity of Shigella sonnei-CRM9 and Shigella flexneri type 2a-rEPAsucc conjugate vaccines in one- to four-year-old children",

abstract = "Background and objective. Shigella conjugate vaccines have been shown to be safe, immunogenic and efficacious in adult volunteers. We have now investigated the safety and immunogenicity of investigational Shigella sonnei and Shigella flexneri 2a conjugate vaccines in 1- to 4-year-old children, the age group at greatest risk for shigellosis. Methods. The O-specific polysaccharides of S. sonnei and S. flexneri 2a, the two most common shigellae from patients in Israel, were bound to medically useful carrier proteins to form conjugates. Eighty healthy 1- to 4-year-olds were randomized to receive two 0.5-ml im injections 6 weeks apart of either S. sonnei-CRM9 or S. flexneri 2a-rEPAsucc. Blood was taken before, 6 weeks after the first injection, 4 weeks after the second injections and 2 years after immunization for assay of IgG anti-lipopolysaccharide, diphtheria toxin and Pseudomonas aeruginosa exotoxin A antibodies by enzyme-linked immunosorbent assay. Results. During an 8-day surveillance period after each immunization, low fever (37.8-39.0°C) lasting only 24 to 48 h occurred in 2 of 40 recipients after the first injection and 4 of 40 recipients after the second injection of S. flexneri 2arEPAsucc and in 2 of 38 of S. sonnei-CRM9 after the second injection; no fever was detected after the first injection. Liver function tests were normal in all vaccinees. S. sonnei-CRM9 elicited a >4-fold rise in IgG anti-LPS in 92.1% and S. flexneri 2a-rEPAsucc in 85% (P < 0.0001) after the second injection; both conjugates elicited type-specific booster responses. At 2 years the geometric mean concentrations of both IgG anti-lipopolysaccharides were significantly higher than preimmunization levels. A >4-fold rise of IgG anti-diphtheria (65.8%) and IgG anti-ETA (77.5%) was observed. Conclusion. These experimental Shigella conjugate vaccines were safe and immunogenic in 1 to 4-year-old children.",

keywords = "Conjugate vaccines, Immunization, Shigellosis",

author = "Passwell, {Justen H.} and Shai Ashkenazi and Efrat Harlev and Dan Miron and Reut Ramon and Nahid Farzam and Liat Lerner-geva and Yonit Levi and Chiayung Chu and Joseph Shiloach and Robbins, {John B.} and Rachel Schneerson",

year = "2003",

month = aug,

day = "1",

doi = "10.1097/01.inf.0000078156.03697.a5",

language = "אנגלית",

volume = "22",

pages = "701--706",

journal = "Pediatric Infectious Disease Journal",

issn = "0891-3668",

publisher = "Lippincott Williams and Wilkins Ltd.",

number = "8",

}

Passwell, JH, Ashkenazi, S, Harlev, E, Miron, D, Ramon, R, Farzam, N, Lerner-geva, L, Levi, Y, Chu, C, Shiloach, J, Robbins, JB & Schneerson, R 2003, 'Safety and immunogenicity of Shigella sonnei-CRM₉ and Shigella flexneri type 2a-rEPA_succ conjugate vaccines in one- to four-year-old children', Pediatric Infectious Disease Journal, vol. 22, no. 8, pp. 701-706. https://doi.org/10.1097/01.inf.0000078156.03697.a5

TY - JOUR

T1 - Safety and immunogenicity of Shigella sonnei-CRM9 and Shigella flexneri type 2a-rEPAsucc conjugate vaccines in one- to four-year-old children

AU - Passwell, Justen H.

AU - Ashkenazi, Shai

AU - Harlev, Efrat

AU - Miron, Dan

AU - Ramon, Reut

AU - Farzam, Nahid

AU - Lerner-geva, Liat

AU - Levi, Yonit

AU - Chu, Chiayung

AU - Shiloach, Joseph

AU - Robbins, John B.

AU - Schneerson, Rachel

PY - 2003/8/1

Y1 - 2003/8/1

N2 - Background and objective. Shigella conjugate vaccines have been shown to be safe, immunogenic and efficacious in adult volunteers. We have now investigated the safety and immunogenicity of investigational Shigella sonnei and Shigella flexneri 2a conjugate vaccines in 1- to 4-year-old children, the age group at greatest risk for shigellosis. Methods. The O-specific polysaccharides of S. sonnei and S. flexneri 2a, the two most common shigellae from patients in Israel, were bound to medically useful carrier proteins to form conjugates. Eighty healthy 1- to 4-year-olds were randomized to receive two 0.5-ml im injections 6 weeks apart of either S. sonnei-CRM9 or S. flexneri 2a-rEPAsucc. Blood was taken before, 6 weeks after the first injection, 4 weeks after the second injections and 2 years after immunization for assay of IgG anti-lipopolysaccharide, diphtheria toxin and Pseudomonas aeruginosa exotoxin A antibodies by enzyme-linked immunosorbent assay. Results. During an 8-day surveillance period after each immunization, low fever (37.8-39.0°C) lasting only 24 to 48 h occurred in 2 of 40 recipients after the first injection and 4 of 40 recipients after the second injection of S. flexneri 2arEPAsucc and in 2 of 38 of S. sonnei-CRM9 after the second injection; no fever was detected after the first injection. Liver function tests were normal in all vaccinees. S. sonnei-CRM9 elicited a >4-fold rise in IgG anti-LPS in 92.1% and S. flexneri 2a-rEPAsucc in 85% (P < 0.0001) after the second injection; both conjugates elicited type-specific booster responses. At 2 years the geometric mean concentrations of both IgG anti-lipopolysaccharides were significantly higher than preimmunization levels. A >4-fold rise of IgG anti-diphtheria (65.8%) and IgG anti-ETA (77.5%) was observed. Conclusion. These experimental Shigella conjugate vaccines were safe and immunogenic in 1 to 4-year-old children.

AB - Background and objective. Shigella conjugate vaccines have been shown to be safe, immunogenic and efficacious in adult volunteers. We have now investigated the safety and immunogenicity of investigational Shigella sonnei and Shigella flexneri 2a conjugate vaccines in 1- to 4-year-old children, the age group at greatest risk for shigellosis. Methods. The O-specific polysaccharides of S. sonnei and S. flexneri 2a, the two most common shigellae from patients in Israel, were bound to medically useful carrier proteins to form conjugates. Eighty healthy 1- to 4-year-olds were randomized to receive two 0.5-ml im injections 6 weeks apart of either S. sonnei-CRM9 or S. flexneri 2a-rEPAsucc. Blood was taken before, 6 weeks after the first injection, 4 weeks after the second injections and 2 years after immunization for assay of IgG anti-lipopolysaccharide, diphtheria toxin and Pseudomonas aeruginosa exotoxin A antibodies by enzyme-linked immunosorbent assay. Results. During an 8-day surveillance period after each immunization, low fever (37.8-39.0°C) lasting only 24 to 48 h occurred in 2 of 40 recipients after the first injection and 4 of 40 recipients after the second injection of S. flexneri 2arEPAsucc and in 2 of 38 of S. sonnei-CRM9 after the second injection; no fever was detected after the first injection. Liver function tests were normal in all vaccinees. S. sonnei-CRM9 elicited a >4-fold rise in IgG anti-LPS in 92.1% and S. flexneri 2a-rEPAsucc in 85% (P < 0.0001) after the second injection; both conjugates elicited type-specific booster responses. At 2 years the geometric mean concentrations of both IgG anti-lipopolysaccharides were significantly higher than preimmunization levels. A >4-fold rise of IgG anti-diphtheria (65.8%) and IgG anti-ETA (77.5%) was observed. Conclusion. These experimental Shigella conjugate vaccines were safe and immunogenic in 1 to 4-year-old children.

KW - Conjugate vaccines

KW - Immunization

KW - Shigellosis

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AN - SCOPUS:0041736184

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JO - Pediatric Infectious Disease Journal

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IS - 8

ER -

Safety and immunogenicity of Shigella sonnei-CRM₉ and Shigella flexneri type 2a-rEPA_succ conjugate vaccines in one- to four-year-old children

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