Safety and immunogenicity of a new Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine in healthy adults

Richmond, Peter; Green, David; Fusco, Peter C.; Fusco, Joan; Heron, Iver; Clark, Sarah L.; Borrow, Raymond; Michon, Francis

doi:10.1016/s0264-410x(99)00276-5

Cited by 98 publications

(69 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Hib and Men C seroconversion and seroprotection rates were compared with control data from other conjugate vaccines. [2][3][4][5][6] Seroconversion was defined as a 4-fold increase in antibody level after vaccination and seroprotection as the minimum antibody level required to protect against disease. 7 Seroprotection and geometric mean titer ratio (GMTR; defined as the geometric mean of individual post-/pre-vaccination titers) control data were available for diphtheria, tetanus, and poliomyelitis vaccine.…”

Section: Methodsmentioning

confidence: 99%

“…3,10 Seroprotection against the novel antigen Men C was low before vaccination, which induced 91% seroprotection and seroconversion in 19 patients (82.6%) (table 2 and figure), similar to rates after other conjugated Men C vaccines. 2,[4][5][6] All patients given diphtheria, tetanus, and poliomyelitis vaccine had seroprotective levels of antibodies to tetanus and diphtheria before and after vaccination, and nearly all were seroprotected against polio (table 2). High prevaccination antibody titers precluded assessment of seroconversion, but GMTRs indicate that responses to diphtheria, tetanus, and poliomyelitis vaccine antigens after alemtuzumab were equivalent to controls (table 2).…”

Section: Serum Igg Antibody Responses To Pneumococcal Polysaccharide mentioning

confidence: 99%

See 1 more Smart Citation

Immune competence after alemtuzumab treatment of multiple sclerosis

et al. 2013

View full text Add to dashboard Cite

Objective: To determine the immunocompetency of patients with multiple sclerosis treated with the lymphodepleting humanized monoclonal antibody alemtuzumab. Methods:In this pilot case-control study, we assessed immunocompetence in 24 patients after alemtuzumab treatment by measuring antibody responses to 3 vaccines (diphtheria, tetanus, and poliomyelitis vaccine, Haemophilus influenzae type b and meningococcal group C conjugate vaccine, and pneumococcal polysaccharide vaccine). In 20 patients, antibodies to common viruses (mumps, rubella, varicella-zoster, and Epstein-Barr virus) were measured before alemtuzumab treatment, then at 1 and 9-11 months after treatment. Results were compared with well-defined historical controls.Results: Serum antibodies against common viruses remained detectable after treatment, and vaccine responses were normal to T-cell-dependent recall antigens (tetanus, diphtheria, and polio), a T-cell-dependent novel antigen (meningococcus C), and T-cell-independent antigens (pneumococcal). There was no evidence for a diminished response to vaccinations in 5 patients studied within 6 months of alemtuzumab treatment. Conclusion:In this small historically controlled pilot study, we demonstrated i) retained humoral immunologic memory (in the form of antibodies against common viruses and response to recall antigens), and ii) the retained ability to mount a humoral immune response against a novel antigen after treatment with alemtuzumab. Classification of evidence:This pilot study provides Class III evidence that patients with relapsingremitting multiple sclerosis appear immunocompetent after treatment with alemtuzumab. Neurology Alemtuzumab is a potential new treatment for relapsing-remitting multiple sclerosis (MS). In a phase II trial, compared with interferon b-1a, alemtuzumab reduced the risks for relapse and sustained accumulation of disability by more than 70% at 3 years, with sustained efficacy at 5 years.1 Two phase III trials (CARE-MS I and CARE-MS II) have confirmed its efficacy in treatment-naive patients, and established superiority over interferon b-1a in patients with disease activity despite first-line therapy. 1Alemtuzumab is a lymphocyte-depleting, anti-CD52 monoclonal antibody. After depletion, cell numbers recover but at varying rates: B cells recover to the lower limit of normal by 7 months, CD81 T cells by 20 months, and CD4 1 T cells by 35 months. 1 After alemtuzumab treatment, the B-cell compartment is composed of naive cells that have emerged from the bone marrow, 1 whereas T cells are largely memory, dominated for 6 months by those with a regulatory phenotype.1 Despite this, infections are not a major concern; in CARE-MS II, the incidence of any infection was 77% after alemtuzumab vs 66% with interferon b-1a, and these were predominantly mild-moderate upper respiratory or urinary tract infections. In contrast,

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Serum Igg Antibody Responses To Pneumococcal Polysaccharide mentioning

confidence: 99%

Immune competence after alemtuzumab treatment of multiple sclerosis

et al. 2013

View full text Add to dashboard Cite

show abstract

“…O-Acetylation of bacterial surface polysaccharides such as CPSs, exopolysaccharides, peptidoglycans, and lipo-oligosaccharides is common in pathogens and in symbionts and has been shown to have immunogenic and functional importance. 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.…”

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

View full text Add to dashboard Cite

“…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

View full text Add to dashboard Cite

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...

show abstract

Safety and immunogenicity of a new Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine in healthy adults

Cited by 98 publications

References 26 publications

Immune competence after alemtuzumab treatment of multiple sclerosis

Immune competence after alemtuzumab treatment of multiple sclerosis

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

Immune Response to Meningococcal Serogroup C Conjugate Vaccine in Asplenic Individuals

Contact Info

Product

Resources

About