Abstract
BackgroundThe Haemophilus influenzae type b (Hib) conjugate vaccine has been widely used in children to prevent invasive Hib disease because of its strong immunogenicity and antibody response induction relative to the capsular polysaccharide (CPS) antigen. The data from vaccine studies suggest that the conjugate vaccine contains carrier proteins that enhance and/or regulate the antigen’s immunogenicity, but the mechanism of this enhancement remains unclear.MethodsTo explore the immunological role of the conjugate vaccine, we compared the immune responses and gene profiles of rhesus macaques after immunization with CPS, carrier protein tetanus toxoid (TT) or conjugate vaccine.ResultsA distinct immune response was induced by the Hib conjugate vaccine but not by CPS or carrier protein TT. The genes that were dynamically regulated in conjunction with the macaque immune responses to the conjugate vaccine were investigated.ConclusionsWe propose that these genes are involved in the induction of specific immunity that is characterized by the appearance and maintenance of antibodies against Hib.
Highlights
The Haemophilus influenzae type b (Hib) conjugate vaccine has been widely used in children to prevent invasive Hib disease because of its strong immunogenicity and antibody response induction relative to the capsular polysaccharide (CPS) antigen
A specific immune response was induced in Hib conjugate vaccine-immunized macaques but not in Hib CPS antigen- or carrier protein tetanus toxoid (TT)-immunized macaques Previous Hib conjugate vaccine trials in human subjects demonstrated good immunogenicity in all immunized pediatric groups after three inoculations, including in children of all ages, whereas the Hib polysaccharide vaccine elicited a lower antibody response in children over 18 months of age [16, 43]
TT could stimulate proliferation of T cells from the monkeys in Hib vaccine group and cytokines secretion (Fig. 1c and d). This result suggests that the Hib conjugate vaccine is capable of eliciting a distinct immune response in 6- to 8-month-old macaques, similar to the effects observed in children older than 18 months of age, whereas the immune response was weak to the polysaccharide antigen
Summary
The Haemophilus influenzae type b (Hib) conjugate vaccine has been widely used in children to prevent invasive Hib disease because of its strong immunogenicity and antibody response induction relative to the capsular polysaccharide (CPS) antigen. 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, in infants and 1-yearolds [1,2,3] This pathogen is associated with purulent meningitis in a specific ratio in all Hib-infected patients [1, 4]. Subsequent Hib conjugate vaccines were developed based on a CPS antigen-binding protein (i.e., diphtheria toxoid (DT), tetanus toxoid (TT) and the N. meningitidies outer membrane protein (OMP) Hib thallus antigen protein) [18, 20] Previous studies of this conjugate vaccine in mice and macaques have shown that remarkable immunity is induced by immunization with this vaccine compared to that induced by the CPS vaccine; the immunity usually presents as an increased antibody response in serum [21]. The increased immunogenicity associated with the Hib conjugate vaccine compared with that of the CPS vaccine suggests that binding of the semi-antigen CPS to the carrier protein would provide an effective antigen for immunization of individuals [27,28,29,30]
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