The Discovery and Development of a Novel Vaccine to Protect against<i>Neisseria meningitidis</i>Serogroup B Disease

Zlotnick, Gary W.; Jones, Thomas R.; Liberator, Paul; Hao, Li; Harris, Shannon L.; McNeil, Lisa K.; Zhu, Duzhang; Perez, John L.; Eiden, Joseph; Jansen, Kathrin U.; Anderson, Annaliesa S.

doi:10.4161/hv.34293

Cited by 81 publications

(70 citation statements)

References 34 publications

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“…However, the common sialic acid-containing epitope of the MnB capsule is also present on human neural tissue, which may explain the poor immunogenicity of the MnB capsule; therefore, out of an abundance of caution, the MnB polysaccharide has not been considered a viable vaccine candidate (30). As a result, protein antigens have been employed in the development of MnB vaccines (31). Two vaccines have recently been licensed for the prevention of MnB disease, namely, Trumenba (bivalent rLP2086) (32) and Bexsero (4CMenB) (33).…”

mentioning

confidence: 99%

Comparison of Phenotypic and Genotypic Approaches to Capsule Typing of Neisseria meningitidis by Use of Invasive and Carriage Isolate Collections

Mohamed

Rojas

et al. 2016

J Clin Microbiol

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e Neisseria meningitidis serogroup B (MnB) is a leading cause of bacterial meningitis; however, MnB is most commonly associated with asymptomatic carriage in the nasopharyngeal cavity, as opposed to the disease state. Two vaccines are now licensed for the prevention of MnB disease; a possible additional benefit of these vaccines could be to protect against disease indirectly by disrupting nasopharyngeal carriage (e.g., herd protection). To investigate this possibility, accurate diagnostic approaches to characterize MnB carriage isolates are required. In contrast to invasive meningococcal disease (IMD) isolates, which can be readily serogrouped, carriage isolates often lack capsule expression, making standard phenotypic assays unsuitable for strain characterization. Several antibody-based methods were evaluated for their abilities to serogroup isolates and were compared with two genotyping methods (real-time PCR [rt-PCR] and whole-genome sequencing [WGS]) to identify which approach would most accurately ascertain the polysaccharide groups associated with carriage isolates. WGS and rt-PCR were in agreement for 99% of IMD isolates, including those with coding sequences for MnB, MnC, MnW, and MnY, and the phenotypic methods correctly identified serogroups for 69 to 98% of IMD isolates. In contrast, only 47% of carriage isolates were groupable by genotypic methods, due to mutations within the capsule operon; of the isolates identified by genotypic methods, <43% were serogroupable with any of the phenotypic methods tested. These observations highlight the difficulties in the serogrouping and capsular genogrouping of meningococcal carriage isolates. Based on our findings, WGS is the most suitable approach for the characterization of meningococcal carriage isolates. N eisseria meningitidis, a Gram-negative bacterium that causes both epidemic and endemic life-threatening disease, is also an obligate human commensal organism that colonizes the nasopharyngeal mucosa with no or minimal harm to the host, a phenomenon known as carriage (1). Asymptomatic pharyngeal colonization with N. meningitidis in young adults is relatively common, and these asymptomatic carriers represent a potential reservoir for the transmission of pathogenic isolates in the community (2, 3). The rates of asymptomatic carriage in the United States and Europe are highest among adolescents and young adults, peaking at the age of 19 years, and are estimated to be 10% to 35% (4-6). Rates of transmission and carriage are higher in closed and semiclosed populations, such as university students living in dormitories and military recruits housed in barracks (7). Higher rates of carriage are also found among people in close contact with patients with active meningococcal infections (8). For the majority of people, carriage is an immunizing process that results in systemic, serogroup-specific, protective antibody responses (9, 10). Invasive meningococcal disease (IMD) usually occurs shortly after the onset of colonization of a susceptible host, when the bacteria ...

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confidence: 99%

Comparison of Phenotypic and Genotypic Approaches to Capsule Typing of Neisseria meningitidis by Use of Invasive and Carriage Isolate Collections

Mohamed

Rojas

et al. 2016

J Clin Microbiol

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“…The development of a universal polysaccharide vaccine including serogroup B was hampered by the striking molecular mimicry in the serogroup B capsule with a component of the human neural cell adhesion molecule (NCAM). [26][27][28] This made a group B polysaccharide poorly immunogenic with risks of autoimmunity and thus efforts focused on developing protein based vaccines, which became recently available. 28 Not until recently has serogroup X emerged as a cause of a number of outbreaks in the meningitis belt threatening with its epidemic potential especially following the introduction of the MenA conjugate vaccine.…”

Section: Prevention Of Diseasementioning

confidence: 99%

“…[26][27][28] This made a group B polysaccharide poorly immunogenic with risks of autoimmunity and thus efforts focused on developing protein based vaccines, which became recently available. 28 Not until recently has serogroup X emerged as a cause of a number of outbreaks in the meningitis belt threatening with its epidemic potential especially following the introduction of the MenA conjugate vaccine. 26,29 Thus, the development of a vaccine against serogroup X has only recently become a public health need and will likely be included in future combination vaccines as serogroup X spreads.…”

Section: Prevention Of Diseasementioning

confidence: 99%

Meningococcal quadrivalent tetanus toxoid conjugate vaccine (MenACWY-TT, Nimenrix™): A review of its immunogenicity, safety, co-administration, and antibody persistence

Assaf-Casals

Dbaibo

2016

Human Vaccines & Immunotherapeutics

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Introduction: Meningococcal disease is a major cause of morbidity and mortality worldwide with reported epidemics and outbreaks in different parts of the world. Despite the availability of antimicrobial therapy, challenges remain in early recognition and prevention of disease. Several vaccines have been developed to date aiming at preventing disease spread. Discussion: MenACWY-TT (Nimenrix TM ) has been extensively studied for use in different age groups. Phase II and III randomized trials have demonstrated its immunogenicity when administered in children aged 1 year and older, adolescents and adults. It has an acceptable safety profile with minor adverse events comparable to other vaccines. Follow up studies have shown persistence of protective antibodies up to three years. MenACWY-TT was safely and effectively coadministered with different recommended vaccines. Conclusion: MenACWY-TT is a safe and immunogenic vaccine that can be used to protect against these four serogroups in individuals older than 1 year of age.

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“…In parallel, a more traditional approach, consisting of fractionation of bacterial extracts and immunological measurements, led to the development of another protein based MenB vaccine, rLP2086 with the commercial name Trumenba ® (Wyeth/Pfizer) [80,81]. This vaccine formulation consists of two lipidated variants of fHbp, which are claimed to cover most circulating MenB strains.…”

Section: Vaccines Against Meningococcal Disease; Status and Perspectivesmentioning

confidence: 99%

Current Trends In Research, Development And Production Of Prophylactic Vaccines: Report of Vaccipharma 2015 Congress

Acevedo

Landys

García-Rivera

et al. 2016

SOJI

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The Discovery and Development of a Novel Vaccine to Protect againstNeisseria meningitidisSerogroup B Disease

Cited by 81 publications

References 34 publications

Comparison of Phenotypic and Genotypic Approaches to Capsule Typing of Neisseria meningitidis by Use of Invasive and Carriage Isolate Collections

Comparison of Phenotypic and Genotypic Approaches to Capsule Typing of Neisseria meningitidis by Use of Invasive and Carriage Isolate Collections

Meningococcal quadrivalent tetanus toxoid conjugate vaccine (MenACWY-TT, Nimenrix™): A review of its immunogenicity, safety, co-administration, and antibody persistence

Current Trends In Research, Development And Production Of Prophylactic Vaccines: Report of Vaccipharma 2015 Congress

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