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Neonatal and infantile immune responses to encapsulated bacteria and conjugate vaccines.

Klein Klouwenberg P, Bont L - Clin. Dev. Immunol. (2008)

Bottom Line: The lack of immune response may be overcome by conjugating the polysaccharides to a carrier protein.This transforms bacterial polysaccharides from a TI-2 antigen into a thymus-dependent (TD) antigen, thereby inducing an immune response and immunological memory in neonates and infants.These and several other approaches in current vaccine development will be discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, University Medical Centre, Room KE4.133.1, PO Box 85090, 3508 AB Utrecht, The Netherlands.

ABSTRACT
Encapsulated bacteria are responsible for the majority of mortality among neonates and infants. The major components on the surface of these bacteria are polysaccharides which are important virulence factors. Immunity against these components protects against disease. However, most of the polysaccharides are thymus-independent (TI)-2 antigens which induce an inadequate immune response in neonates and infants. The mechanisms that are thought to play a role in the unresponsiveness of this age group to TI-2 stimuli will be discussed. The lack of immune response may be overcome by conjugating the polysaccharides to a carrier protein. This transforms bacterial polysaccharides from a TI-2 antigen into a thymus-dependent (TD) antigen, thereby inducing an immune response and immunological memory in neonates and infants. Such conjugated vaccines have been shown to be effective against the most common causes of invasive disease caused by encapsulated bacteria in neonates and children. These and several other approaches in current vaccine development will be discussed.

Show MeSH
Schematic diagram of mechanism of action of PS and PS-protein conjugate vaccines. (a) Polysaccharide vaccines stimulate marginal zone B-cells which will proliferate in loco and differentiate into short-living plasma cells, which are responsible for the rapid release of low-affinity antibodies and thus first-line defence against the pathogen; (b) conjugate vaccines stimulate B-blasts that will migrate into the germinal centre, where they proliferate, undergo somatic hypermutations and isotype class switch, and differentiate into either long-living plasma cells (that produce high-affinity antibodies) and memory B cells. Abbreviations: CD40L (CD40 ligand), GC (germinal centre), MZ (marginal zone), DC (dendritic cell), MZ DC (marginal zone dendritic cell).
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fig1: Schematic diagram of mechanism of action of PS and PS-protein conjugate vaccines. (a) Polysaccharide vaccines stimulate marginal zone B-cells which will proliferate in loco and differentiate into short-living plasma cells, which are responsible for the rapid release of low-affinity antibodies and thus first-line defence against the pathogen; (b) conjugate vaccines stimulate B-blasts that will migrate into the germinal centre, where they proliferate, undergo somatic hypermutations and isotype class switch, and differentiate into either long-living plasma cells (that produce high-affinity antibodies) and memory B cells. Abbreviations: CD40L (CD40 ligand), GC (germinal centre), MZ (marginal zone), DC (dendritic cell), MZ DC (marginal zone dendritic cell).

Mentions: The impaired neonatal and infantile immuneresponse to polysaccharide vaccines can be circumvented by conjugating thepolysaccharide to a protein carrier [37–39], based on the old dogma that haptenswhen attached to a protein carrier can induce an immune response. The mechanismby which a polysaccharide-protein conjugate vaccine acts is depicted in Figure 1. Today, all current polysaccharide vaccines registered for children below agetwo are conjugated vaccines. Conjugates transform bacterial polysaccharidesfrom a TI-2 antigen into a TD-antigen and thereby induce an immune response andimmunological memory in neonates [40], however not to theextend as in adults [4]. Several factors which are relatedespecially to immunizations might contribute to a suboptimal response toconjugate vaccines. Firstly, the route of immunization determines the recallresponse to polysaccharides in mice that have been vaccinated with a conjugateas neonates [41]. Secondly, the choice of type ofprotein conjugate is important and determines the amount of IgG antibodyresponse [41]. Lastly,in neonatal mice there is a Th-2 skew which leads to a predominantly IgG1response and impaired IgG2a antibody formation [4], the latter thought to be moreprotective against encapsulated bacteria [6].


Neonatal and infantile immune responses to encapsulated bacteria and conjugate vaccines.

Klein Klouwenberg P, Bont L - Clin. Dev. Immunol. (2008)

Schematic diagram of mechanism of action of PS and PS-protein conjugate vaccines. (a) Polysaccharide vaccines stimulate marginal zone B-cells which will proliferate in loco and differentiate into short-living plasma cells, which are responsible for the rapid release of low-affinity antibodies and thus first-line defence against the pathogen; (b) conjugate vaccines stimulate B-blasts that will migrate into the germinal centre, where they proliferate, undergo somatic hypermutations and isotype class switch, and differentiate into either long-living plasma cells (that produce high-affinity antibodies) and memory B cells. Abbreviations: CD40L (CD40 ligand), GC (germinal centre), MZ (marginal zone), DC (dendritic cell), MZ DC (marginal zone dendritic cell).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2553187&req=5

fig1: Schematic diagram of mechanism of action of PS and PS-protein conjugate vaccines. (a) Polysaccharide vaccines stimulate marginal zone B-cells which will proliferate in loco and differentiate into short-living plasma cells, which are responsible for the rapid release of low-affinity antibodies and thus first-line defence against the pathogen; (b) conjugate vaccines stimulate B-blasts that will migrate into the germinal centre, where they proliferate, undergo somatic hypermutations and isotype class switch, and differentiate into either long-living plasma cells (that produce high-affinity antibodies) and memory B cells. Abbreviations: CD40L (CD40 ligand), GC (germinal centre), MZ (marginal zone), DC (dendritic cell), MZ DC (marginal zone dendritic cell).
Mentions: The impaired neonatal and infantile immuneresponse to polysaccharide vaccines can be circumvented by conjugating thepolysaccharide to a protein carrier [37–39], based on the old dogma that haptenswhen attached to a protein carrier can induce an immune response. The mechanismby which a polysaccharide-protein conjugate vaccine acts is depicted in Figure 1. Today, all current polysaccharide vaccines registered for children below agetwo are conjugated vaccines. Conjugates transform bacterial polysaccharidesfrom a TI-2 antigen into a TD-antigen and thereby induce an immune response andimmunological memory in neonates [40], however not to theextend as in adults [4]. Several factors which are relatedespecially to immunizations might contribute to a suboptimal response toconjugate vaccines. Firstly, the route of immunization determines the recallresponse to polysaccharides in mice that have been vaccinated with a conjugateas neonates [41]. Secondly, the choice of type ofprotein conjugate is important and determines the amount of IgG antibodyresponse [41]. Lastly,in neonatal mice there is a Th-2 skew which leads to a predominantly IgG1response and impaired IgG2a antibody formation [4], the latter thought to be moreprotective against encapsulated bacteria [6].

Bottom Line: The lack of immune response may be overcome by conjugating the polysaccharides to a carrier protein.This transforms bacterial polysaccharides from a TI-2 antigen into a thymus-dependent (TD) antigen, thereby inducing an immune response and immunological memory in neonates and infants.These and several other approaches in current vaccine development will be discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, University Medical Centre, Room KE4.133.1, PO Box 85090, 3508 AB Utrecht, The Netherlands.

ABSTRACT
Encapsulated bacteria are responsible for the majority of mortality among neonates and infants. The major components on the surface of these bacteria are polysaccharides which are important virulence factors. Immunity against these components protects against disease. However, most of the polysaccharides are thymus-independent (TI)-2 antigens which induce an inadequate immune response in neonates and infants. The mechanisms that are thought to play a role in the unresponsiveness of this age group to TI-2 stimuli will be discussed. The lack of immune response may be overcome by conjugating the polysaccharides to a carrier protein. This transforms bacterial polysaccharides from a TI-2 antigen into a thymus-dependent (TD) antigen, thereby inducing an immune response and immunological memory in neonates and infants. Such conjugated vaccines have been shown to be effective against the most common causes of invasive disease caused by encapsulated bacteria in neonates and children. These and several other approaches in current vaccine development will be discussed.

Show MeSH