Hib Vaccines: Past, Present, and Future Perspectives

Abstract

Haemophilus influenzae type b (Hib) causes many severe diseases, including epiglottitis, pneumonia, sepsis, and meningitis. In developed countries, the annual incidence of meningitis caused by bacteria is approximately 5–10 cases per population of 100,000. The Hib conjugate vaccine is considered protective and safe. Adjuvants, molecules that can enhance and/or regulate the fundamental immunogenicity of an antigen, comprise a wide range of diverse compounds. While earlier developments of adjuvants created effective products, there is still a need to create new generations, rationally designed based on recent discoveries in immunology, mainly in innate immunity. Many factors may play a role in the immunogenicity of Hib conjugate vaccines, such as the polysaccharides and proteins carrier used in vaccine construction, as well as the method of conjugation. A Hib conjugate vaccine has been constructed via chemical synthesis of a Hib saccharide antigen. Two models of carbohydrate-protein conjugate have been established, the single ended model (terminal amination-single method) and cross-linked lattice matrix (dual amination method). Increased knowledge in the fields of immunology, molecular biology, glycobiology, glycoimmunology, and the biology of infectious microorganisms has led to a dramatic increase in vaccine efficacy.

Convenient synthesis of the pentasaccharide repeating unit corresponding to the cell wall O-antigen of Escherichia albertii O4

“…Recently, Naumenko et al [11] reported the structure of the repeating unit of the cell wall O-polysaccharide of the E. albertii O4 strain [11], which is a pentasaccharide comprising of α-linked ᴅ-galactosamine, β-linked ᴅ-glucosamine, β-linked ᴅ-galactose, α-linked ʟ-fucose and α-linked ʟ-rhamnose moieties. In the recent past, several vaccine candidates have been developed to control bacterial infections by conjugating cell wall polysaccharides with suitable proteins, which include vaccines against Haemophilia influenza type b (Hib) [12,13], meningitis [14], pneumococcal infections [15,16] and enteric diseases such as cholera [17], diarrhea [18] and urinary tract infections [19]. Despite the possibility of isolating the polysaccharides by fermentation techniques, it is difficult to get a significant quantity of polysaccharide fragments from natural sources with adequate purity.…”

A modular synthetic route to size-defined immunogenicHaemophilus influenzaeb antigens is key to the identification of an octasaccharide lead vaccine candidate

“…1 ) and possesses the highest invasive potential among encapsulated H. influenzae ; thus, it is a major health concern, especially for children. 3 …”

RNA gene profile variation in peripheral blood mononuclear cells from rhesus macaques immunized with Hib conjugate vaccine, Hib capsular polysaccharide and TT carrier protein

“…Haemophilus influenzae type b (Hib) is a widely recognized member of the Haemophilus genus that directly causes respiratory infectious disease with characteristic manifestations of tympanitis, bronchitis and pneumonia in children of all ages, particularly in infants and 1-year-olds [ 1 – 3 ]. Notably, this pathogen is associated with purulent meningitis in a specific ratio in all Hib-infected patients [ 1 , 4 ].…”

“…Haemophilus influenzae type b (Hib) is a widely recognized member of the Haemophilus genus that directly causes respiratory infectious disease with characteristic manifestations of tympanitis, bronchitis and pneumonia in children of all ages, particularly in infants and 1-year-olds [ 1 – 3 ]. Notably, this pathogen is associated with purulent meningitis in a specific ratio in all Hib-infected patients [ 1 , 4 ]. Epidemiological studies of this pathogen have primarily been performed in developed countries and have shown that the incidence in children under the age of 5 in areas such as the US, France, and Switzerland is approximately 20–100/100,000 [ 5 – 9 ], but few data have been reported for developing areas.…”

“…Although no systematic, epidemiological study of Hib has been performed in mainland China, studies of this pathogen in a small number of populations in different regions of China have indicated that the potential incidence of pediatric infections in mainland China is noteworthy [ 10 , 11 ]. Numerous studies have addressed Hib structure and immunology [ 12 , 13 ], leading to the licensure of a preventive vaccine against Hib infection in the 1980s [ 1 ]. Based on the results of a structural study of the Hib agent that suggested that the bacterium presented a capsular polysaccharide (CPS) antigen and thallus antigen, the early vaccine was prepared with polyribosylribitol phosphate (PRP), which is composed of ribosylribitol phosphate as the basic unit [ 14 , 15 ].…”