Investigating the candidacy of a capsular polysaccharide-based glycoconjugate as a vaccine to combat Haemophilus influenzae type a disease: A solution for an unmet public health need

Cox, Andrew D.; Williams, Dean T.; Cairns, Chantelle M.; Michael, Frank St.; Fleming, Perry; Vinogradov, Evgeny; Arbour, Mélanie; Masson, Luke; Zou, Wei

doi:10.1016/j.vaccine.2017.09.055

Cited by 27 publications

(19 citation statements)

References 25 publications

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“…This hypothesis was corroborated by recent conjugation of sized and activated Hia polysaccharide to CRM 197 and protein D as carriers (Cox et al. 2017 ). The glycoconjugates were immunogenic in rabbits and elicited bactericidal antibodies.…”

Section: Approaches For Production Of Glycoconjugate Vaccinessupporting

confidence: 54%

Potential targets for next generation antimicrobial glycoconjugate vaccines

Micoli¹,

Costantino

Adamo

2018

FEMS Microbiology Reviews

139

109

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Cell surface carbohydrates have been proven optimal targets for vaccine development. Conjugation of polysaccharides to a carrier protein triggers a T-cell-dependent immune response to the glycan moiety. Licensed glycoconjugate vaccines are produced by chemical conjugation of capsular polysaccharides to prevent meningitis caused by meningococcus, pneumococcus and Haemophilus influenzae type b. However, other classes of carbohydrates (O-antigens, exopolysaccharides, wall/teichoic acids) represent attractive targets for developing vaccines. Recent analysis from WHO/CHO underpins alarming concern toward antibiotic-resistant bacteria, such as the so called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) and additional pathogens such as Clostridium difficile and Group A Streptococcus. Fungal infections are also becoming increasingly invasive for immunocompromised patients or hospitalized individuals. Other emergencies could derive from bacteria which spread during environmental calamities (Vibrio cholerae) or with potential as bioterrorism weapons (Burkholderia pseudomallei and mallei, Francisella tularensis). Vaccination could aid reducing the use of broad-spectrum antibiotics and provide protection by herd immunity also to individuals who are not vaccinated.This review analyzes structural and functional differences of the polysaccharides exposed on the surface of emerging pathogenic bacteria, combined with medical need and technological feasibility of corresponding glycoconjugate vaccines.

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Section: Approaches For Production Of Glycoconjugate Vaccinessupporting

confidence: 54%

Potential targets for next generation antimicrobial glycoconjugate vaccines

Micoli¹,

Costantino

Adamo

2018

FEMS Microbiology Reviews

139

109

View full text Add to dashboard Cite

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“…Nevertheless, our findings suggest a conserved nature of protective epitopes recognized by bactericidal antibodies that may be explained by the uniform composition of Hia capsular PS, a polymer of glucose and ribitol connected by phosphodiester linkages [ 47 ]. Among others, we tested an isolate (11–139, ST-23), of which a polysaccharide antigen was used for the development of Hia vaccine candidate, and this isolate showed similar sensitivity to serum bactericidal effect as 13–155 (ST-62) and 13–240 (ST-4) suggesting that antibodies stimulated by immunization with the antigen from a vaccine candidate strain will be protective against various Hia bacteria [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Characterization of natural bactericidal antibody against Haemophilus influenzae type a in Canadian First Nations: A Canadian Immunization Research Network (CIRN) Clinical Trials Network (CTN) study

et al. 2018

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During the last two decades, Haemophilus influenzae serotype a (Hia) emerged as an important cause of invasive disease in Canadian First Nations and Inuit, and Alaskan Native populations, with the highest rates reported in young children. Immunocompetent adults, in contrast to children, do not typically develop invasive Hia disease. To clarify factors responsible for an increased burden of invasive Hia disease in certain population groups we studied serum bactericidal activity (SBA) against Hia and quantified IgG and IgM specific to Hia capsular polysaccharide in healthy adult members of two First Nations communities: 1) with reported cases of invasive Hia disease (Northern Ontario, NO), and 2) without reported cases (Southern Ontario, SO), in comparison to non-First Nations living in proximity to the NO First Nations community, and non-First Nations elderly non-frail Canadians from across the country (total of 110 First Nations and 76 non-First Nations). To elucidate the specificity of bactericidal antibodies, sera were absorbed with various Hia antigens. Naturally acquired SBA against Hia was detected at higher rates in First Nations (NO, 80%; SO, 96%) than non-First Nations elderly Canadians (64%); the SBA titres in First Nations were higher than in non-First Nations elderly Canadians (P<0.001) and NO non-First Nations adults (P>0.05). Among First Nations, SBA was mediated predominantly by IgM, and by both antibodies specific to Hia capsular polysaccharide and lipooligosaccharide. Conclusions: The SBA against Hia is frequently present in sera of First Nations adults regardless of the burden of Hia disease observed in their community; it may represent part of the natural antibody repertoire, which is potentially formed in this population under the influence of certain epigenetic factors. Although the nature of these antibodies deserves further studies to understand their origin, the data suggest that they may represent important protective mechanism against invasive Hia disease.

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“…The development of a vaccine against Hia is of particular concern for Indigenous communities in the northern regions of Canada and Alaska, for which an emergence of Hia infections has been observed over the last decades [40]. A capsular polysaccharide-based glycoconjugate vaccine has shown promising results, but its development is still in very early stages [120].…”

Section: Expert Opinionmentioning

confidence: 99%

Haemophilus influenzae type b disease in the era of conjugate vaccines: critical factors for successful eradication

Slack

Esposito

Haas

et al. 2020

Expert Review of Vaccines

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Introduction: Prior to implementation of Haemophilus influenzae type b (Hib)-conjugate vaccination programs in the 1990s, Hib was the commonest cause of bacterial meningitis in children aged <5 years. While the burden of all Hib disease has significantly decreased in the post-vaccination era, Hib still accounted for >29,000 deaths worldwide in children aged <5 years in 2015. Areas covered: We reviewed literature data on the most widely used Hib vaccines and vaccination strategies which led to the global prevention and control of Hib disease and aim to highlight important factors for continued disease control and elimination in the future. Expert commentary: More than 90% of countries worldwide have implemented Hib-conjugate vaccination in their national immunization programs. Vaccines containing Hib polyribosylribitol phosphate (PRP) conjugated with tetanus toxoid (Hib-TT) are the most commonly used. Neisseria meningitidis outer membrane protein complex of PRP (Hib-OMP) is also used. Although the kinetics of the immune response varies with Hib vaccine and schedule used, high control of Hib disease was observed in all settings/scenarios. Further improving global Hib vaccination coverage may result in disease elimination.

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Investigating the candidacy of a capsular polysaccharide-based glycoconjugate as a vaccine to combat Haemophilus influenzae type a disease: A solution for an unmet public health need

Cited by 27 publications

References 25 publications

Potential targets for next generation antimicrobial glycoconjugate vaccines

Potential targets for next generation antimicrobial glycoconjugate vaccines

Characterization of natural bactericidal antibody against Haemophilus influenzae type a in Canadian First Nations: A Canadian Immunization Research Network (CIRN) Clinical Trials Network (CTN) study

Haemophilus influenzae type b disease in the era of conjugate vaccines: critical factors for successful eradication

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