scholarly journals Conjugate vaccines for enteric fever: proceedings of a meeting organized in New Delhi, India in 2009

2010 ◽  
Vol 4 (06) ◽  
pp. 404-411 ◽  
Author(s):  
Audino Podda ◽  
Allan James Saul ◽  
Rashmi Arora ◽  
Zulfiqar Bhutta ◽  
Anju Sinha ◽  
...  
Keyword(s):  
South Asia ◽  
Conjugate Vaccine ◽  
Enteric Fever ◽  
Vaccine Development ◽  
Severe Disease ◽  
Age Groups ◽  
New Combination ◽  
Conjugate Vaccines ◽  
Vaccination Programs ◽  
Young Infants

Enteric fever is responsible for significant morbidity in South Asia and high prevalence of severe disease is seen in children under two years of age. Effective typhoid vaccines are available, but they cannot be used for children under two years of age and also have some limitations in older age groups. Participants supported development of a Salmonella Typhi conjugate vaccine able to induce effective, long-lasting immunity in young children. The role of Salmonella Paratyphi A as a cause of enteric fever was discussed and consensus reached that a bivalent S. Typhi-S. Paratyphi A conjugate vaccine is highly desirable; however, considering disease epidemiology and the advanced status of vaccine development, rapid introduction of monovalent S. Typhi conjugate vaccine into vaccination programs of South Asia was recommended. Prevention should be emphasized, available vaccines used, and efforts toward improving sanitation continued. Success of the new vaccine will depend on several factors, including delivery costs and governmental ability to adopt and implement suitable immunization programs. To ensure good immunization coverage, the conjugate vaccine could be administered either to young infants, concomitantly with infant EPI vaccines, or to older infants, concomitantly with measles vaccine, currently given at 9 to 12 months. The need for new combination vaccines, containing both EPI and typhoid antigens, was discussed as a tool to increase coverage and reduce the number of injections and priority conflicts in a crowded infant vaccination schedule. However, stand-alone enteric fever conjugate vaccines would allow more flexibility to immunize different age groups and therefore should be rapidly developed.

scholarly journals Impact and effectiveness of meningococcal vaccines: a review

2017 ◽  
Vol 41 ◽  
pp. 1
Author(s):  
Lucia Helena De Oliveira ◽  
Barbara Jauregui ◽  
Ana Flavia Carvalho ◽  
Norberto Giglio
Keyword(s):  
Conjugate Vaccine ◽  
Meningococcal Disease ◽  
Age Groups ◽  
Epidemiological Surveillance ◽  
Surveillance Systems ◽  
Protein Subunit ◽  
Conjugate Vaccines ◽  
Vaccination Programs ◽  
Meta Analyses ◽  
The Impact

Objectives.To summarize and critically evaluate the evidence on the impact and effectiveness of meningococcal vaccination programs around the world in order to inform decisionmaking in Latin America and the Caribbean.Methods.A review of the literature was conducted following several components of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed Central® was searched for papers published in any language from January 1999 – March 2017.Results.In all, 32 studies were included, most of which evaluated the meningococcal C conjugate vaccine. Fourteen studies measured effectiveness and 30 measured impact. The effectiveness of polysaccharide vaccines was 65% – 83.7% (different age groups), while the effectiveness of the conjugate vaccines was 66% – 100%. Incidence decline of laboratory-confirmed meningococcal disease for the conjugate vaccine ranged from 77% – 100% among different ages groups. The only study that evaluated the protein subunit vaccine reported a vaccine effectiveness of 82.9%.Conclusions.The studies reviewed show impact and effectiveness of both polysaccharide vaccines and conjugate vaccines on vaccine-serogroup meningococcal disease. The conjugate vaccines, however, show higher impact and effectiveness with longer-lasting protection over the polysaccharide vaccines. Given the variance in potential use of a meningococcal vaccine, epidemiological surveillance systems should be strengthened to inform national decisions.

scholarly journals Vaccines against Meningococcal Diseases

2020 ◽  
Vol 8 (10) ◽  
pp. 1521
Author(s):  
Mariagrazia Pizza ◽  
Rafik Bekkat-Berkani ◽  
Rino Rappuoli
Keyword(s):  
Conjugate Vaccine ◽  
Meningococcal Disease ◽  
Vaccine Development ◽  
Health Concern ◽  
Global Public Health ◽  
Public Health Concern ◽  
Conjugate Vaccines ◽  
Vaccination Programs ◽  
Meningitis Belt ◽  
Life Threatening

Neisseria meningitidis is the main cause of meningitis and sepsis, potentially life-threatening conditions. Thanks to advancements in vaccine development, vaccines are now available for five out of six meningococcal disease-causing serogroups (A, B, C, W, and Y). Vaccination programs with monovalent meningococcal serogroup C (MenC) conjugate vaccines in Europe have successfully decreased MenC disease and carriage. The use of a monovalent MenA conjugate vaccine in the African meningitis belt has led to a near elimination of MenA disease. Due to the emergence of non-vaccine serogroups, recommendations have gradually shifted, in many countries, from monovalent conjugate vaccines to quadrivalent MenACWY conjugate vaccines to provide broader protection. Recent real-world effectiveness of broad-coverage, protein-based MenB vaccines has been reassuring. Vaccines are also used to control meningococcal outbreaks. Despite major improvements, meningococcal disease remains a global public health concern. Further research into changing epidemiology is needed. Ongoing efforts are being made to develop next-generation, pentavalent vaccines including a MenACWYX conjugate vaccine and a MenACWY conjugate vaccine combined with MenB, which are expected to contribute to the global control of meningitis.

scholarly journals Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Jacqueline M. Miller ◽  
Narcisa Mesaros ◽  
Marie Van Der Wielen ◽  
Yaela Baine
Keyword(s):  
Global Health ◽  
Haemophilus Influenzae ◽  
Neisseria Meningitidis ◽  
Conjugate Vaccine ◽  
Age Groups ◽  
Type B ◽  
Conjugate Vaccines ◽  
Age Related ◽  
New Vaccines ◽  
Infants And Young Children

Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection againstHaemophilus influenzaetype b andNeisseria meningitidisserogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which addsN. meningitidisserogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT) designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles.

scholarly journals Biosynthesis of Conjugate Vaccines Using an O-Linked Glycosylation System

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Chao Pan ◽  
Peng Sun ◽  
Bo Liu ◽  
Haoyu Liang ◽  
Zhehui Peng ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Neisseria Meningitidis ◽  
Conjugate Vaccine ◽  
Vaccine Development ◽  
Rapid Development ◽  
Protein Glycosylation ◽  
Major Histocompatibility ◽  
Protein Subunit ◽  
Conjugate Vaccines ◽  
Histocompatibility Complex

ABSTRACT Conjugate vaccines are known to be one of the most effective and safest types of vaccines against bacterial pathogens. Previously, vaccine biosynthesis has been performed by using N-linked glycosylation systems. However, the structural specificity of these systems for sugar substrates has hindered their application. Here, we report a novel protein glycosylation system (O-linked glycosylation viaNeisseria meningitidis) that can transfer virtually any glycan to produce a conjugate vaccine. We successfully established this system inShigellaspp., avoiding the construction of an expression vector for polysaccharide synthesis. We further found that different protein substrates can be glycosylated using this system and that the O-linked glycosylation system can also effectively function in other Gram-negative bacteria, including some strains whose polysaccharide structure was not suitable for conjugation using the N-linked glycosylation system. The results from a series of animal experiments show that the conjugate vaccine produced by this O-linked glycosylation system offered a potentially protective antibody response. Furthermore, we elucidated and optimized the recognition motif, named MOOR, for theO-glycosyltransferase PglL. Finally, we demonstrated that the fusion of other peptides recognized by major histocompatibility complex class II around MOOR had no adverse effects on substrate glycosylation, suggesting that this optimized system will be useful for future vaccine development. Our results expand the glycoengineering toolbox and provide a simpler and more robust strategy for producing bioconjugate vaccines against a variety of pathogens.IMPORTANCERecently, the rapid development of synthetic biology has allowed bioconjugate vaccines with N-linked protein glycosylation to become a reality. However, the difficulty of reestablishing the exogenous polysaccharide synthetic pathway inEscherichia colihinders their application. Here, we show that an O-linked protein glycosylation system fromNeisseria meningitidis, which has a lower structure specificity for sugar substrates, could be engineered directly in attenuated pathogens to produce effective conjugate vaccines. To facilitate the further design of next-generation bioconjugate vaccines, we optimized a novel short motif consisting of 8 amino acids that is sufficient for glycosylation. Our results expand the application potential of O-linked protein glycosylation and demonstrate a simpler and more robust strategy for producing bioconjugate vaccines against different pathogens. In the future, bacterial antigenic polysaccharides could be attached to major histocompatibility complex binding peptides to improve immunological memory or attached to protein subunit vaccine candidates to provide double immune stimulation.

scholarly journals Eliminating Meningococcal Epidemics From the African Meningitis Belt: The Case for Advanced Prevention and Control Using Next-Generation Meningococcal Conjugate Vaccines

2019 ◽  
Vol 220 (Supplement_4) ◽  
pp. S274-S278 ◽  
Author(s):  
Mark R Alderson ◽  
F Marc LaForce ◽  
Ajoke Sobanjo-ter Meulen ◽  
Angela Hwang ◽  
Marie-Pierre Preziosi ◽  
...  
Keyword(s):  
Conjugate Vaccine ◽  
Prevention And Control ◽  
Vaccine Development ◽  
Next Generation ◽  
Meningococcal Infections ◽  
Conjugate Vaccines ◽  
Meningitis Belt ◽  
And Control ◽  
New Vaccines

AbstractThe introduction and rollout of a meningococcal serogroup A conjugate vaccine, MenAfriVac, in the African meningitis belt has eliminated serogroup A meningococcal infections for >300 million Africans. However, serogroup C, W, and X meningococci continue to circulate and have been responsible for focal epidemics in meningitis belt countries. Affordable multivalent meningococcal conjugate vaccines are being developed to prevent these non-A epidemics. This article describes the current epidemiologic situation and status of vaccine development and highlights questions to be addressed to most efficiently use these new vaccines.

scholarly journals Changing Epidemiology of Bacterial Meningitis Since Introduction of Conjugate Vaccines: Three Decades of National Meningitis Surveillance in The Netherlands

2020 ◽  
Author(s):  
Diederik L H Koelman ◽  
Merel N van Kassel ◽  
Merijn W Bijlsma ◽  
Matthijs C Brouwer ◽  
Diederik van de Beek ◽  
...  
Keyword(s):  
The Netherlands ◽  
Bacterial Meningitis ◽  
Group B Streptococcus ◽  
Age Groups ◽  
Haemophilus Influenzae Type ◽  
Acute Bacterial Meningitis ◽  
Residual Rate ◽  
Conjugate Vaccines ◽  
Young Infants ◽  
The Impact

Abstract Background The epidemiology of acute bacterial meningitis has changed substantially since the introduction of conjugate vaccines. Methods We analysed nationwide surveillance data of all cerebrospinal fluid isolates received from 1988 to 2019 in the Netherlands. We assessed the impact of conjugate vaccines on incidence (defined as episodes per 100,000 population per year) and for different age groups using incidence rate ratios (IRR), comparing incidence before and after conjugate vaccine introduction. Results We analysed 17,393 episodes of which 5,960 episodes (34%) occurred in pre-school children (3 months-4 years). Overall, bacterial meningitis incidence decreased from 6.37 to 1.58 between 1989-1993 and 2014-2019 (IRR 0.25 [95%CI 0.23-0.26], p<0.001), and was most pronounced in pre-school and school-aged children (5-15 years; IRR 0.10 [95%CI 0.09-0.12] and 0.08 [95%CI 0.06-0.10], both p<0.001). The incidence was highest in young infants (<90 days) due to a high incidence of group B streptococcus and Escherichia coli meningitis (42.48 and 19.49). Conjugate vaccines effectively reduced the incidence of Haemophilus influenzae type b, Neisseria meningitidis serogroup C, and 10 pneumococcal serotypes (IRR 0.02-0.04, p<0.001). At the end of the observed period, Streptococcus pneumoniae caused the majority of meningitis cases (829/1,616 [51%]), mostly in older adults (45-64 years) and elderly (65+ years; incidence 1.06 and 1.54, respectively). Conclusions Conjugate vaccines reduced the burden of bacterial meningitis, especially in children. The efforts for new measures to prevent bacterial meningitis should be focused on neonates and elderly, as the residual rate of disease is still high in these age groups.

scholarly journals Strategies for active and passive pediatric RSV immunization

2021 ◽  
Vol 9 ◽  
pp. 251513552098151
Author(s):  
Katherine M. Eichinger ◽  
Jessica L. Kosanovich ◽  
Madeline Lipp ◽  
Kerry M. Empey ◽  
Nikolai Petrovsky
Keyword(s):  
Vaccine Development ◽  
Severe Disease ◽  
Time Frame ◽  
Protein Antigens ◽  
Young Infants ◽  
Immunization Strategies ◽  
Number Of Factors ◽  
Syncytial Virus ◽  
Tract Infections ◽  
Short Time

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in children worldwide, with the most severe disease occurring in very young infants. Despite half a century of research there still are no licensed RSV vaccines. Difficulties in RSV vaccine development stem from a number of factors, including: (a) a very short time frame between birth and first RSV exposure; (b) interfering effects of maternal antibodies; and (c) differentially regulated immune responses in infants causing a marked T helper 2 (Th2) immune bias. This review seeks to provide an age-specific understanding of RSV immunity critical to the development of a successful pediatric RSV vaccine. Historical and future approaches to the prevention of infant RSV are reviewed, including passive protection using monoclonal antibodies or maternal immunization strategies versus active infant immunization using pre-fusion forms of RSV F protein antigens formulated with novel adjuvants such as Advax that avoid excess Th2 immune polarization.

scholarly journals Epidemiology and Trends of Pertussis among Infants: United States, 2000–2015

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S5-S5 ◽  
Author(s):  
Catherine Bozio ◽  
Tami Skoff ◽  
Tracy Pondo ◽  
Jennifer Liang
Keyword(s):  
Negative Binomial ◽  
Severe Disease ◽  
Age Distribution ◽  
Age Groups ◽  
Case Fatality ◽  
Annual Average ◽  
Young Infants ◽  
Hospitalization Rates ◽  
The Impact ◽  
Over Time

Abstract Background Pertussis, a cyclic respiratory disease, causes the greatest morbidity and mortality among infants, particularly those too young to be vaccinated. Following a resurgence of pertussis in the 1990s, a recommendation was made in 2012 to vaccinate during every pregnancy in order to prevent infant disease. We describe pertussis trends from 2000–2015 among U.S. infants aged <1 year. Methods We analyzed infant pertussis cases reported through the National Notifiable Diseases Surveillance System from 2000 to 2015. Incidence rates (cases per 100,000 population) among various age groups (<2, 2– <4, 4– <6, and 6–<12 months) were calculated using National Center for Health Statistics population estimates as denominators. Negative binomial regression was used to estimate the annual average percent change with a linear trend; P < 0.05 was significant. Results From 2000 to 2015, 48,909 infant pertussis cases and 255 deaths were reported; infants aged <2 months accounted for 38.7% of cases. The age distribution of infant cases was stable from 2000 to 2009 but changed from 2010 to 2015 (Fig. 1), as the proportion of cases aged 4–<12 months increased annually on average by 4.7% (P < 0.001). Annual incidence was highest among <2 month olds; however, rates increased among older infants (Fig. 2): 7% average annual increase among infants aged 4–<6 months and 11% among infants aged 6–<12 months (P < 0.001 for each). The proportion of infants hospitalized decreased over time in each age group (P < 0.001 for all) with the largest annual average declines among 4–<6 (−5.1%) and 6–<12 month (−5.9%) olds. For all age groups, hospitalization rates were relatively stable, but non-hospitalization rates increased (P < 0.05 for all). The case–fatality ratio (CFR) was highest among <2 month olds (1.6%); CFRs decreased over time among <2 and 2–< 4 month olds (P < 0.05 for each). Conclusion Pertussis incidence remains highest among infants aged <4 months, although the age distribution appears to be changing. Decreasing proportions of infants hospitalized may suggest a true decline in disease severity or an increase in reporting of less severe disease. Ongoing monitoring of infant pertussis is needed to better understand the impact of vaccinating pregnant women to prevent pertussis in young infants. Disclosures All authors: No reported disclosures.

scholarly journals Serotype Replacement After the Introduction of the 13-valent Pneumococcal Conjugate Vaccine in Ontario, Canada, 2007-2018

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Allison H Yeung ◽  
Shinthuja Wijayasri ◽  
Sarah E Wilson ◽  
Tara M Harris ◽  
Sarah A Buchan ◽  
...  
Keyword(s):  
Public Health ◽  
Severe Disease ◽  
Age Groups ◽  
Pneumococcal Vaccination ◽  
Case Fatality ◽  
Vaccination Programs ◽  
Hospitalization Rates ◽  
Age Related ◽  
Serotype Replacement ◽  
Vaccine Type

Introduction: Invasive pneumococcal disease (IPD) is a disease of public health significance in Ontario, Canada, where publicly funded pneumococcal vaccination programs target children, older adults, and people at high risk of disease. Since the implementation of pneumococcal conjugate vaccines (PCV), serotype replacement has been documented, where non-PCV serotypes replace the niche created by the reduction in vaccine-preventable serotypes. Our objective was to determine whether there has been serotype replacement or a change in IPD severity in Ontario since implementation of the childhood 13-valent (PCV13) program by assessing IPD burden over a 12-year period (2007-2018). Methods: We included all confirmed IPD cases reported in Ontario’s integrated Public Health Information System (iPHIS) and defined the pre-PCV13 era (January 2007-December 2010) and post-PCV13 era (January 2011-December 2018). We grouped IPD serotypes according to associated vaccine type: PCV13; 23-valent polysaccharide vaccine (unique PPV23); and non-vaccine-preventable (NVP). We used population data to calculate incidence and hospitalization rates (per 100,000 population) by age group, vaccine type, and era. Results: In the post-PCV13 era, PCV13-specific incidence and hospitalization rates decreased, while the incidence and hospitalizations due to unique PPV23 and NVP serotypes increased; this was consistent across all age groups. The greatest decrease in incidence (RR=0.4) and hospitalizations (RR=0.4) was observed in children <5 years with PCV13 serotypes. There were no distinct age-related trends observed for case fatality ratios; the highest CFR was observed in adults ≥65 years. Conclusion: A shift in serotype distribution was seen across all age groups; IPD incidence and hospitalization rates due to PCV13 serotypes decreased after PCV13 implementation, but this reduction was offset by the increasing burden and severity of unique PPV23 and NVP serotypes. As IPD continues to be a severe disease, continued surveillance is required to better understand the growing burden of these serotypes and emergence of non-vaccine-preventable serotypes.

scholarly journals Structural and immunological characterization of E. coli derived recombinant CRM197 protein used as carrier in conjugate vaccines

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Ravi P.N. Mishra ◽  
Ravi S.P. Yadav ◽  
Christopher Jones ◽  
Salvatore Nocadello ◽  
George Minasov ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Conjugate Vaccine ◽  
Vaccine Development ◽  
Structural Characteristics ◽  
Data Bank ◽  
Carrier Protein ◽  
Regulatory Requirements ◽  
Conjugate Vaccines ◽  
E Coli

It is established that the immunogenicity of polysaccharides is enhanced by coupling them to carrier proteins. Cross reacting material (CRM197), a nontoxic variant of diphtheria toxin (DT) is widely used carrier protein for polysaccharide conjugate vaccines. Conventionally, CRM197 is isolated by fermentation of Corynebacterium diphtheriae C7 (β197) cultures, which often suffers from low yield. Recently, several recombinant approaches have been reported with robust processes and higher yields, which will improve the affordability of CRM197-based vaccines. Vaccine manufacturers require detailed analytical information to ensure that the CRM197 meets quality standards and regulatory requirements. In the present manuscript we have described detailed structural characteristics of Escherichia coli based recombinant CRM197 (rCRM197) carrier protein. The crystal structure of the E. coli based rCRM197 was found to be identical with the reported crystal structure of the C7 CRM197 produced in C. diphtheriae C7 strain (Protein Data Bank (PDB) ID: 4EA0). The crystal structure of rCRM197 was determined at 2.3 Å resolution and structure was submitted to the PDB with accession number ID 5I82. This is the first report of a crystal structure of E. coli derived recombinant CRM197 carrier protein. Furthermore, the rCRM197 was conjugated to Vi polysaccharide to generate Typhoid conjugate vaccine (Vi-rCRM197) and its immunogenicity was evaluated in Balb/C Mice. The Vi-rCRM197 conjugate vaccine was found to generate strong primary α-Vi antibody response and also showed a booster response after subsequent vaccination in mice. Overall data suggest that E. coli based recombinant CRM197 exhibits structural and immunological similarity with the C7 CRM197 and can be used as a carrier protein in conjugate vaccine development.

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