Glycoconjugate Vaccines for Prevention of Haemophilus influenzae Type b Diseases

Khatuntseva, Elena A.; Nifantiev, Nikolay E.

doi:10.1134/s1068162021010106

Cited by 10 publications

(3 citation statements)

References 149 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the Hib antigen, instability was observed in all the formulations at both 2–8 °C ( Figure 6 D) and accelerated storage conditions (15 °C and 25 °C) ( Figure 6 H,L), with the most destabilization seen in the AH-only hexavalent formulation. This loss of antibody binding of the Hib antigen over time is likely due to the known interaction of the negatively charged Hib antigen with the positively charged AH adjuvant, leading to steric hinderances as well as chemical instabilities [ 34 , 35 ]. Overall, these results indicate the t-NRRV antigens have no effect on the stability of the four pentavalent antigens.…”

Section: Resultsmentioning

confidence: 99%

Evaluating the Compatibility of New Recombinant Protein Antigens (Trivalent NRRV) with a Mock Pentavalent Combination Vaccine Containing Whole-Cell Pertussis: Analytical and Formulation Challenges

Kumar,

Holland,

Secrist

et al. 2024

Vaccines

View full text Add to dashboard Cite

Introducing new recombinant protein antigens to existing pediatric combination vaccines is important in improving coverage and affordability, especially in low- and middle-income countries (LMICs). This case-study highlights the analytical and formulation challenges encountered with three recombinant non-replicating rotavirus vaccine (NRRV) antigens (t-NRRV formulated with Alhydrogel® adjuvant, AH) combined with a mock multidose formulation of a pediatric pentavalent vaccine used in LMICs. This complex formulation contained (1) vaccine antigens (i.e., whole-cell pertussis (wP), diphtheria (D), tetanus (T), Haemophilus influenza (Hib), and hepatitis B (HepB), (2) a mixture of aluminum-salt adjuvants (AH and Adju-Phos®, AP), and (3) a preservative (thimerosal, TH). Selective, stability-indicating competitive immunoassays were developed to monitor binding of specific mAbs to each antigen, except wP which required the setup of a mouse immunogenicity assay. Simple mixing led to the desorption of t-NRRV antigens from AH and increased degradation during storage. These deleterious effects were caused by specific antigens, AP, and TH. An AH-only pentavalent formulation mitigated t-NRRV antigen desorption; however, the Hib antigen displayed previously reported AH-induced instability. The same rank-ordering of t-NRRV antigen stability (P[8] > P[4] > P[6]) was observed in mock pentavalent formulations and with various preservatives. The lessons learned are discussed to enable future multidose, combination vaccine formulation development with new vaccine candidates.

show abstract

Section: Resultsmentioning

confidence: 99%

Evaluating the Compatibility of New Recombinant Protein Antigens (Trivalent NRRV) with a Mock Pentavalent Combination Vaccine Containing Whole-Cell Pertussis: Analytical and Formulation Challenges

Kumar,

Holland,

Secrist

et al. 2024

Vaccines

View full text Add to dashboard Cite

show abstract

“…PRP was conjugated to a diphtheria toxoid (DT) protein in 1983, resulting in the first glycoconjugate vaccine ever developed. , Currently, different Hib glycoconjugate vaccines with different carrier proteins are available on the EU and US market, either in single form or in combination with other vaccines (Table ). , Quimi-Hib ( 1 , Figure ) is based on a synthetic PRP and has been licensed in Cuba in 2004. It is composed of a synthetic antigen with an average of seven RP repeating units conjugated to a thiolated TT carrier protein through a 3-(maleimido)-propylamide linker .…”

Section: Improving Existing Vaccinesmentioning

confidence: 99%

Synthetic Glycans to Improve Current Glycoconjugate Vaccines and Fight Antimicrobial Resistance

Bino

Østerlid

et al. 2022

Chem. Rev.

View full text Add to dashboard Cite

Antimicrobial resistance (AMR) is emerging as the next potential pandemic. Different microorganisms, including the bacteria Acinetobacter baumannii, Clostridioides diff icile, Escherichia coli, Enterococcus faecium, Klebsiella pneumoniae, Neisseria gonorrhoeae, Pseudomonas aeruginosa, non-typhoidal Salmonella, and Staphylococcus aureus, and the fungus Candida auris, have been identified by the WHO and CDC as urgent or serious AMR threats. Others, such as group A and B Streptococci, are classified as concerning threats. Glycoconjugate vaccines have been demonstrated to be an efficacious and cost-effective measure to combat infections against Haemophilus inf luenzae, Neisseria meningitis, Streptococcus pneumoniae, and, more recently, Salmonella typhi. Recent times have seen enormous progress in methodologies for the assembly of complex glycans and glycoconjugates, with developments in synthetic, chemoenzymatic, and glycoengineering methodologies. This review analyzes the advancement of glycoconjugate vaccines based on synthetic carbohydrates to improve existing vaccines and identify novel candidates to combat AMR. Through this literature survey we built an overview of structure−immunogenicity relationships from available data and identify gaps and areas for further research to better exploit the peculiar role of carbohydrates as vaccine targets and create the next generation of synthetic carbohydrate-based vaccines.

show abstract

“…In the pre-vaccine era, H. influenzae type b (Hib) contributed substantially to the burden of meningitis and other life-threatening infections in young children in the USA and Europe [3,4], while the other serotypes were considered non-invasive. After the conjugate Hib vaccine [5][6][7][8][9][10] was introduced into childhood immunization schedules, an epidemiological shift to other strains belonging to serotypes H. influenzae type a (Hia) [11][12][13][14][15][16], e [11,17], and f [11,18] was observed worldwide.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Pseudooligosaccharides Related to the Capsular Phosphoglycan of Haemophilus influenzae Type a

et al. 2023

View full text Add to dashboard Cite

Synthesis of spacer-armed pseudodi-, pseudotetra-, and pseudohexasaccharides related to the capsular phosphoglycan of Haemophilus influenzae type a, the second most virulent serotype of H. influenzae (after type b), was performed for the first time via iterative chain elongation using H-phosphonate chemistry for the formation of inter-unit phosphodiester bridges. These compounds were prepared for the design of neoglycoconjugates, as exemplified by the transformation of the obtained pseudohexasaccharide derivative into a biotinylated glycoconjugate suitable for use in immunological studies, particularly in diagnostic screening systems as a coating antigen for streptavidin-coated plates and chip slides.

show abstract

Glycoconjugate Vaccines for Prevention of Haemophilus influenzae Type b Diseases

Cited by 10 publications

References 149 publications

Evaluating the Compatibility of New Recombinant Protein Antigens (Trivalent NRRV) with a Mock Pentavalent Combination Vaccine Containing Whole-Cell Pertussis: Analytical and Formulation Challenges

Evaluating the Compatibility of New Recombinant Protein Antigens (Trivalent NRRV) with a Mock Pentavalent Combination Vaccine Containing Whole-Cell Pertussis: Analytical and Formulation Challenges

Synthetic Glycans to Improve Current Glycoconjugate Vaccines and Fight Antimicrobial Resistance

Synthesis of Pseudooligosaccharides Related to the Capsular Phosphoglycan of Haemophilus influenzae Type a

Contact Info

Product

Resources

About