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      Progress toward the global control of Neisseria meningitidis: 21st century vaccines, current guidelines, and challenges for future vaccine development

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          ABSTRACT

          The control of meningitis, meningococcemia and other infections caused by Neisseria meningitidis is a significant global health challenge. Substantial progress has occurred in the last twenty years in meningococcal vaccine development and global implementation. Meningococcal protein-polysaccharide conjugate vaccines to serogroups A, C, W, and Y (modeled after the Haemophilus influenzae b conjugate vaccines) provide better duration of protection and immunologic memory, and overcome weak immune responses in infants and young children and hypo-responsive to repeated vaccine doses seen with polysaccharide vaccines. ACWY conjugate vaccines also interfere with transmission and reduce nasopharyngeal colonization, thus resulting in significant herd protection. Advances in serogroup B vaccine development have also occurred using conserved outer membrane proteins with or without OMV as vaccine targets. Challenges for meningococcal vaccine research remain including developing combination vaccines containing ACYW(X) and B, determining the ideal booster schedules for the conjugate and MenB vaccines, and addressing issues of waning effectiveness.

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          Most cited references103

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          Epidemic meningitis, meningococcaemia, and Neisseria meningitidis.

          Meningococcus, an obligate human bacterial pathogen, remains a worldwide and devastating cause of epidemic meningitis and sepsis. However, advances have been made in our understanding of meningococcal biology and pathogenesis, global epidemiology, transmission and carriage, host susceptibility, pathophysiology, and clinical presentations. Approaches to diagnosis, treatment, and chemoprophylaxis are now in use on the basis of these advances. Importantly, the next generation of meningococcal conjugate vaccines for serogroups A, C, Y, W-135, and broadly effective serogroup B vaccines are on the horizon, which could eliminate the organism as a major threat to human health in industrialised countries in the next decade. The crucial challenge will be effective introduction of new meningococcal vaccines into developing countries, especially in sub-Saharan Africa, where they are urgently needed.
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            Meningococcal disease.

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              Impact of meningococcal serogroup C conjugate vaccines on carriage and herd immunity.

              In 1999, meningococcal serogroup C conjugate (MCC) vaccines were introduced in the United Kingdom for those under 19 years of age. The impact of this intervention on asymptomatic carriage of meningococci was investigated to establish whether serogroup replacement or protection by herd immunity occurred. Multicenter surveys of carriage were conducted during vaccine introduction and on 2 successive years, resulting in a total of 48,309 samples, from which 8599 meningococci were isolated and characterized by genotyping and phenotyping. A reduction in serogroup C carriage (rate ratio, 0.19) was observed that lasted at least 2 years with no evidence of serogroup replacement. Vaccine efficacy against carriage was 75%, and vaccination had a disproportionate impact on the carriage of sequence type (ST)-11 complex serogroup C meningococci that (rate ratio, 0.06); these meningococci also exhibited high rates of capsule expression. The impact of vaccination with MCC vaccine on the prevalence of carriage of group C meningococci was consistent with herd immunity. The high impact on the carriage of ST-11 complex serogroup C could be attributed to high levels of capsule expression. High vaccine efficacy against disease in young children, who were not protected long-term by the schedule initially used, is attributed to the high vaccine efficacy against carriage in older age groups.
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                Author and article information

                Journal
                Hum Vaccin Immunother
                Hum Vaccin Immunother
                KHVI
                khvi20
                Human Vaccines & Immunotherapeutics
                Taylor & Francis
                2164-5515
                2164-554X
                2018
                9 May 2018
                9 May 2018
                : 14
                : 5
                : 1146-1160
                Affiliations
                Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine , Atlanta, GA, USA
                Author notes
                CONTACT D. S. Stephens, MD dstep01@ 123456emory.edu Emory School of Medicine , Atlanta GA 30322
                Article
                1451810
                10.1080/21645515.2018.1451810
                6067816
                29543582
                e182c572-d9f8-458c-b713-903c056e4b84
                © 2018 The Author(s). Published with license by Taylor & Francis

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.

                History
                : 7 December 2017
                : 21 February 2018
                : 9 March 2018
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 147, Pages: 15
                Funding
                Support was provided by CDC Emerging Infections Programs.
                Categories
                Review

                Molecular medicine
                neisseria meningitidis,meningitis,meningococcemia,polysaccharide- protein conjugate vaccine,polysaccharide vaccines,epidemiology

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