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

Dretler, Alexandra W.; Rouphael, Nadine; Stephens, David S.

doi:10.1080/21645515.2018.1451810

Cited by 65 publications

(58 citation statements)

References 122 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With the advancement of new antibody-discovery technologies (immune receptor identification), we believe that this promises to be a rapidly growing field in the near future. Generation of complement-activating antibodies is also considered important for the protective action of multivalent Neisseria vaccines that trigger the formation of antibodies that kill bacteria via MAC or phagocytosis [64,65]. A potent vaccine candidate in N. meningitidis is factor H-binding protein (fHBP), an outer membraneassociated lipoprotein that recruits factor H and thereby downregulates complement activation.…”

Section: Exploiting the Action Of Complement In Immune Therapies Agaimentioning

confidence: 99%

Complement and Bacterial Infections: From Molecular Mechanisms to Therapeutic Applications

et al. 2018

View full text Add to dashboard Cite

Complement is a complex protein network of plasma, and an integral part of the innate immune system. Complement activation results in the rapid clearance of bacteria by immune cells, and direct bacterial killing via large pore-forming complexes. Here we review important recent discoveries in the complement field, focusing on interactions relevant for the defense against bacteria. Understanding the molecular interplay between complement and bacteria is of great importance for future therapies for infectious and inflammatory diseases. Antibodies that support complement-dependent bacterial killing are of interest for the development of alternative therapies to treat infections with antibiotic-resistant bacteria. Furthermore, a variety of novel therapeutic complement inhibitors have been developed to prevent unwanted complement activation in autoimmune inflammatory diseases. A better understanding of how such inhibitors may increase the risk of bacterial infections is essential if such therapies are to be successful.

show abstract

Section: Exploiting the Action Of Complement In Immune Therapies Agaimentioning

confidence: 99%

Complement and Bacterial Infections: From Molecular Mechanisms to Therapeutic Applications

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Polysaccharide-conjugated vaccines, based on isolated CPS antigens attached to carrier proteins, protect young children and the elderly from deadly bacterial pathogens including Haemophilus influenzae type b (Hib), Neisseria meningitides, and the encapsulated gram-positive bacterium Streptococcus pneumoniae. S. pneumoniae is the leading cause of life-endangering diseases such as pneumonia, septicemia, and meningitis (1), and a major cause of death in children under five in developing countries (2)(3)(4). More than 90 S. pneumoniae serotypes can be distinguished based on their CPS (5,6).…”

mentioning

confidence: 99%

Improving vaccines against Streptococcus pneumoniae using synthetic glycans

Kapłonek

Khan

Reppe

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Streptococcus pneumoniae remains a deadly disease in small children and the elderly even though conjugate and polysaccharide vaccines based on isolated capsular polysaccharides (CPS) are successful. The most common serotypes that cause infection are used in vaccines around the world, but differences in geographic and demographic serotype distribution compromises protection by leading vaccines. The medicinal chemistry approach to glycoconjugate vaccine development has helped to improve the stability and immunogenicity of synthetic vaccine candidates for several serotypes leading to the induction of higher levels of specific protective antibodies. Here, we show that marketed CPS-based glycoconjugate vaccines can be improved by adding synthetic glycoconjugates representing serotypes that are not covered by existing vaccines. Combination (coformulation) of synthetic glycoconjugates with the licensed vaccines Prevnar13 (13-valent) and Synflorix (10-valent) yields improved 15-and 13-valent conjugate vaccines, respectively, in rabbits. A pentavalent semisynthetic glycoconjugate vaccine containing five serotype antigens (sPCV5) elicits antibodies with strong in vitro opsonophagocytic activity. This study illustrates that synthetic oligosaccharides can be used in coformulation with both isolated polysaccharide glycoconjugates to expand protection from existing vaccines and each other to produce precisely defined multivalent conjugated vaccines. synthetic glycans | vaccine | Streptococcus pneumoniae C apsular polysaccharides (CPS) surround many deadly human pathogens. Polysaccharide-conjugated vaccines, based on isolated CPS antigens attached to carrier proteins, protect young children and the elderly from deadly bacterial pathogens including Haemophilus influenzae type b (Hib), Neisseria meningitides, and the encapsulated gram-positive bacterium Streptococcus pneumoniae. S. pneumoniae is the leading cause of life-endangering diseases such as pneumonia, septicemia, and meningitis (1), and a major cause of death in children under five in developing countries (2-4). More than 90 S. pneumoniae serotypes can be distinguished based on their CPS (5, 6). Currently available CPS-based pneumococcal vaccines contain the serotypes most frequently associated with invasive pneumococcal diseases (IPDs). Although the licensed 23-valent polysaccharide vaccine (Pneumovax 23) is not effective in younger children (3, 7), the conjugate vaccines Prevnar13 and Synflorix cover 13 and 10 serotypes, respectively, and are highly successful in all age groups (8). Nevertheless, serotype replacement due to vaccination and regional differences in dominant serotypes necessitate the expansion of existing vaccines to include additional serotypes. An additional weak point is that some serotype antigens, such as ST5 and ST1, that are present in existing vaccines undergo undesired chemical modification during production (9, 10); others have limited immunogenicity and lead to protective levels well below those required for herd immunity, such as SP3 (6).The p...

show abstract

“…The replacement of monovalent MenC vaccines with MenACWY vaccines, broadening the range of protection, is expected in the coming years, particularly in middle-and highincome countries. In addition, the pentavalent (MenACWYX) conjugate vaccine will likely be licensed within the next 5 years and is planned for widespread use across sub-Saharan Africa [77].…”

Section: Expert Opinionmentioning

confidence: 99%

Protecting the most vulnerable age group: a review of MenACWY-TT immunogenicity and safety in infants

Martinón-Torres

Serra

Sáfadi

2020

Expert Review of Vaccines

View full text Add to dashboard Cite

Introduction: Neisseria meningitidis causes invasive meningococcal disease (IMD), with the highest incidence observed in infants and young children. Meningococcal serogroups A, B, C, W, X, and Y account for almost all IMD cases worldwide. Available meningococcal vaccines targeting serogroups A, C, W, and Y (MenACWY) include those conjugated to diphtheria toxoid (MenACWY-D), diphtheria protein cross-reactive material 197 (MenACWY-CRM 197 ), and tetanus toxoid (MenACWY-TT). MenACWY-TT is indicated for use starting at 6 weeks of age. Areas covered: This review discusses data from the four primary studies assessing MenACWY-TT safety and immunogenicity in infants, which evaluated a variety of dosing schedules, short-term and longterm outcomes, and impact of coadministration on the immunogenicity of routine childhood vaccines. Remaining gaps in the field are addressed. Expert opinion: Robust data support the use of MenACWY-TT in infants starting as early as 6 weeks of age. MenACWY-TT was safe and well tolerated in infants, was immunogenic after priming and booster, and demonstrated persistent immunogenicity. Lower persistence for serogroup A relative to other serogroups based on serum bactericidal assays (SBAs) using human complement appears to be a class effect of MenACWY conjugate vaccines. Correlates of protection other than SBA are being explored, including immunologic responses associated with different carrier proteins. ARTICLE HISTORY

show abstract

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

Cited by 65 publications

References 122 publications

Complement and Bacterial Infections: From Molecular Mechanisms to Therapeutic Applications

Complement and Bacterial Infections: From Molecular Mechanisms to Therapeutic Applications

Improving vaccines against Streptococcus pneumoniae using synthetic glycans

Protecting the most vulnerable age group: a review of MenACWY-TT immunogenicity and safety in infants

Contact Info

Product

Resources

About