Evaluation of De-O-Acetylated Meningococcal C Polysaccharide-Tetanus Toxoid Conjugate Vaccine in Infancy: Reactogenicity, Immunogenicity, Immunologic Priming, and Bactericidal Activity against O-Acetylated and De-O-Acetylated Serogroup C Strains

Richmond, Peter; Borrow, Ray; Findlow, Jamie; Martin, Sarah; Thornton, Carol A.; Cartwright, Keith; Miller, Elizabeth

doi:10.1128/iai.69.4.2378-2382.2001

Cited by 89 publications

(73 citation statements)

References 32 publications

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“…The MCC vaccines were shown to be safe and immunogenic in infants following the 2/3/4 month schedule [11][12][13]18] and in adolescents [19]. The hyporesponsiveness reported following meningococcal polysaccharide vaccines in young children and adults is overcome by administration of the MCC vaccine [15,17,20].…”

Section: Pre-licensure Studiesmentioning

confidence: 99%

“…Following promising results in infants vaccinated under the UK 2/3/4 month schedule [11][12][13], the DH initiated further clinical trials to answer key policy-related questions. These trials determined the schedule to be used for catch-up immunisation of older age groups [14], the effect of prior vaccination with plain meningococcal C polysaccharide used for outbreak control on the response to MCC vaccines [15][16][17], and the compatibility of MCC vaccines when given at the same time as other vaccines used in the UK schedule, in particular diphtheria and tetanus vaccines which are similar to the carrier proteins in the MCC vaccines [1].…”

Section: Pre-licensure Studiesmentioning

confidence: 99%

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Impact of meningococcal C conjugate vaccine in the UK

Balmer¹,

Borrow²,

Miller

2002

Journal of Medical Microbiology

213

120

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Section: Pre-licensure Studiesmentioning

confidence: 99%

Section: Pre-licensure Studiesmentioning

confidence: 99%

Impact of meningococcal C conjugate vaccine in the UK

Balmer¹,

Borrow²,

Miller

2002

Journal of Medical Microbiology

213

120

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“…N. meningitidis, E. coli K1, Streptococcus pneumoniae, S. enterica, S. aureus, and Pseudomonas aeruginosa can express O-acetylated CPS (32,33). In S. enterica serovar typhi (7) and E. coli K1 (6), the loss of O-acetylation from CPS results in loss of immunogenicity, whereas in meningococcal serogroup C (31) and pneumococcal serotype 9V (34), O-acetylation of capsules is not required for induction of protective antibodies. In the extracellular alginate polysaccharide polymers, produced by isolates of P. aeruginosa from patients with cystic fibrosis, Dmannuronic acid is O-acetylated at O-2 and O-3 by three genes, algI, algJ, and algF (35).…”

Section: Figmentioning

confidence: 99%

The Neisseria meningitidis Serogroup A Capsular Polysaccharide O-3 and O-4 Acetyltransferase

Gudlavalleti¹,

Datta

Tzeng³

et al. 2004

Journal of Biological Chemistry

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“…Meningococcal serogroup C plain polysaccharide vaccines are not immunogenic in those under the age of 2 years (13,17), and repeated doses can lead to hyporesponsiveness (2,13,18,29). MCC vaccines that have been shown to be highly immunogenic and to generate immune memory in all age groups from infants to adults are now available (10,(25)(26)(27)(28)(29). MCC vaccines have been shown to be efficacious in all the age groups targeted during the vaccination campaign initiated in 1999 in the United Kingdom and elicit herd immunity (23).…”

mentioning

confidence: 99%

Immune Response to Meningococcal Serogroup C Conjugate Vaccine in Asplenic Individuals

Balmer¹,

Falconer

McDonald

et al. 2004

Infect Immun

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Asplenic individuals are known to be at increased risk of infection with encapsulated bacteria. Recent United Kingdom recommendations stated that this at-risk group should receive one dose of the meningococcal serogroup C conjugate (MCC) vaccine. However, the immune response of asplenic individuals to MCC vaccine is unknown. The immune response of asplenics (n ‫؍‬ 130) to immunization with the MCC vaccine was investigated. Asplenic individuals had a significantly lower geometric mean titer (GMT) (157.8; 95% confidence interval [CI], 94.5 to 263.3) of bactericidal antibody in serum (SBA) than an age-matched control group (n ‫؍‬ 48) (1448.2; 95% CI, 751.1 to 2792.0). However, 80% of asplenic individuals achieved the proposed protective SBA titer of >8. No differences were observed between the two groups in the serogroup C-specific immunoglobulin G geometric mean concentration. A significant reduction in SBA GMT or the number of responders achieving an SBA titer of >8 was observed if the reason for splenectomy was a medical cause or if MCC vaccination occurred <10 years after splenectomy. Individuals (n ‫؍‬ 29) who did not achieve an SBA titer of >16 were offered a second dose of MCC vaccine. Analysis of the SBA response revealed that 61% (14 of 23) of the individuals who received a second dose achieved a protective titer. In total, 93% of asplenic individuals achieved a titer of >8 following MCC vaccination (one or two doses combined). We recommend that, following vaccination of asplenics, either the level of functional antibody should be determined, with a second dose of MCC vaccine offered to nonresponders, or two doses of MCC vaccine should be routinely offered.Asplenic individuals are at an increased risk of infection from encapsulated bacteria, including Neisseria meningitidis (9, 15). Overwhelming postsplenectomy infection has a high mortality rate, between 40% and 70% (7). Immunization with the 23-valent pneumococcal plain polysaccharide and Haemophilus influenzae type b (Hib) conjugate (29) vaccines is recommended for individuals with functional or anatomic asplenia. In 2001, the United Kingdom Department of Health extended this recommendation to include vaccination with meningococcal serogroup C conjugate (MCC) vaccine, although no data on immune responses are available to date for MCC vaccines in this group (6).Various studies have provided conflicting evidence on the immune response to polysaccharide antigens in asplenic individuals (12, 21), and the limitations of plain polysaccharide vaccines are well documented (13,17,18,29). Meningococcal serogroup C plain polysaccharide vaccines are not immunogenic in those under the age of 2 years (13, 17), and repeated doses can lead to hyporesponsiveness (2,13,18,29). MCC vaccines that have been shown to be highly immunogenic and to generate immune memory in all age groups from infants to adults are now available (10, 25-29). MCC vaccines have been shown to be efficacious in all the age groups targeted during the vaccination campaign initiated in 1999 in the Uni...

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Evaluation of De-O-Acetylated Meningococcal C Polysaccharide-Tetanus Toxoid Conjugate Vaccine in Infancy: Reactogenicity, Immunogenicity, Immunologic Priming, and Bactericidal Activity against O-Acetylated and De-O-Acetylated Serogroup C Strains

Cited by 89 publications

References 32 publications

Impact of meningococcal C conjugate vaccine in the UK

Impact of meningococcal C conjugate vaccine in the UK

The Neisseria meningitidis Serogroup A Capsular Polysaccharide O-3 and O-4 Acetyltransferase

Immune Response to Meningococcal Serogroup C Conjugate Vaccine in Asplenic Individuals

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