: Quadrivalent meningococcal conjugate vaccine (Menactra [MenACWY-D]), was licensed in the United States in 2005 to prevent meningococcal disease in adolescents and adults. The license was extended to children aged 2-10 years in 2007 and extended again in 2011 to infants aged 9 months and older based, in part, on results from 3 phase III studies presented herein.
: The safety and immunogenicity of 2 doses of MenACWY-D was assessed in study-eligible children: dose 1 was administered at 9 months of age and dose 2 was administered 3 months later with or without routine childhood vaccines.
: Thirty days after vaccination, protective serum bactericidal assay-human complement titers ≥1:8 for meningococcal serogroups A, C, Y and W-135 were achieved by 86-100% of children receiving 2 doses of MenACWY-D. When MenACWY-D was concomitantly administered with measles, mumps, rubella and varicella or heptavalent pneumococcal conjugate vaccine, 81-98% of participants achieved protective responses (serum bactericidal assay-human complement titers ≥1:8 for all serogroups). All seroprotection rates were >91% when the protective titer was defined as serum bactericidal assay-human complement ≥1:4. MenACWY-D did not interfere with measles, mumps, rubella or varicella vaccine responses (98-100% achieved protective titers). When heptavalent pneumococcal conjugate vaccine was given concomitantly with MenACWY-D, antipneumococcal antibody levels, although decreased, were protective for all serotypes by enzyme-linked immunosorbent assay (98-100% ≥ 0.35 μg/mL) and opsonophagocytic assay (99-100% ≥ 1:8). Adverse events were generally mild and similar across groups. Serious adverse events were uncommon.
: MenACWY-D was safe and immunogenic when given in 2 doses to infants and toddlers; this vaccine can be given with other common childhood immunizations.
"For the meningococcus, the introduction of vaccines against serogroups W, Y and X is required. Some tetravalent (A, C, W, Y) vaccines are available  and there are moves to produce inexpensive versions of these for use in Africa with the MVP model. Serogroup B meningococci present more of a problem with little prospect of a conjugate polysaccharide vaccine against them owing to safety concerns . "
[Show abstract][Hide abstract] ABSTRACT: The development and implementation of conjugate polysaccharide vaccines against invasive bacterial diseases, specifically those caused by the encapsulated bacteria Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae, has been one of the most effective public health innovations of the last 25 years. These vaccines have resulted in significant reductions in childhood morbidity and mortality worldwide, with their effectiveness due in large part to their ability to induce long-lasting immunity in a range of age groups. At the population level this immunity reduces carriage and interrupts transmission resulting in herd immunity; however, these beneficial effects can be counterbalanced by the selection pressures that immunity against carriage can impose, potentially promoting the emergence and spread of virulent vaccine escape variants. Studies following the implementation of meningococcal serogroup C vaccines improved our understanding of these effects in relation to the biology of accidental pathogens such as the meningococcus. This understanding has enabled the refinement of the implementation of conjugate polysaccharide vaccines against meningitis-associated bacteria, and will be crucial in maintaining and improving vaccine control of these infections. To date there is little evidence for the spread of virulent vaccine escape variants of the meningococcus and H. influenzae, although this has been reported in pneumococci.
Philosophical Transactions of The Royal Society B Biological Sciences 08/2013; 368(1623):20120147. DOI:10.1098/rstb.2012.0147 · 7.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: CME EDUCATIONAL OBJECTIVES 1. Review the current epidemiology of meningococcal disease in children. 2. Discuss the history of meningococcal vaccine development and the unique challenges posed by developing a vaccine against this microbe. 3. Determine vaccine recommendations as well as potential roadblocks to routine vaccination of young children. The spectrum of disease caused by Neisseria meningitidis includes bacteremia, fulminant sepsis (meningococcemia), meningitis, and pneumonia. The incidence of meningococcal infection has long been higher in infancy than adolescents or adults older than 65 years (a third group with an increased risk based on age). Five meningococcal serogroups (A, B, C, Y, and W135) cause the great majority of human disease. Serogroup B strains cause about two-thirds of disease in children younger than 6 years. For this reason, new meningococcal vaccine formulations have been developed and evaluated in children younger than 2 years. Of four meningococcal vaccines currently licensed in the United States, two conjugate products, (MenACWY-D [Menactra], Sanofi Pasteur; HibMenCY-TT [MenHibrix], GlaxoSmithKline), are recommended for infants and toddlers younger than 2 years who have an increased risk for invasive meningococcal disease. High-risk conditions are complement deficiencies, community outbreaks, functional or anatomic asplenia, and travel to high-risk areas in which serogroup A infection is prevalent. Recommendations vary by age, dosing, and indication between these two products. Both licensed products are immunogenic and have side-effect profiles that are considered safe for use. In most cases, concomitant use with other recommended childhood vaccines does not interfere with responses to these vaccines. As of yet, there has not been universal adoption of this immunization in the infant population by parents or providers. Factors that weigh against the implementation of a national routine infant program include the prevention of only 40 to 50 meningococcal cases, two to four deaths per year, and a relatively low case fatality among infants. Some argue that costs should not be considered a barrier because infant deaths and morbidity would be prevented. The availability of a serogroup B vaccine would improve impact and cost-effectiveness of a routine infant meningococcal vaccine program. Debate over the implementation of routine infant meningococcal vaccination in the United States is ongoing. This review focuses on vaccines for the prevention of N. meningitidis infection in infants and young toddlers in the first 2 years of life.
[Show abstract][Hide abstract] ABSTRACT: The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.