Elderly Immune Response to a TI‐2 Antigen: Heavy and Light Chain Use and Bactericidal Activity to<i>Neisseria meningitidis</i>Serogroup C Polysaccharide

Hutchins, Wendy; Carlone, George M.; Westerink, M. A. Julie

doi:10.1086/314750

Cited by 16 publications

(17 citation statements)

References 61 publications

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“…We observed a predominantly IgG2 response to MCP, with less IgG1 and almost no IgG3 or IgG4 whether the antigen was delivered nasally or parenterally. This pattern has been observed in studies of parenteral immunization with MCP (18,19). In contrast, CRM197-specific IgG subclasses were mixed, with equal levels of IgG1 and IgG2 and high levels of IgG4 in many subjects, probably indicating repeated boosting.…”

Section: Discussionsupporting

confidence: 62%

Induction of Protective Serum Meningococcal Bactericidal and Diphtheria-Neutralizing Antibodies and Mucosal Immunoglobulin A in Volunteers by Nasal Insufflations of theNeisseria meningitidisSerogroup C Polysaccharide-CRM197 Conjugate Vaccine Mixed with Chitosan

et al. 2005

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Thirty-six healthy volunteers received either a single intramuscular injection of Neisseria meningitidis serogroup C polysaccharide (MCP)-CRM197 conjugate vaccine in alum or two nasal insufflations 28 days apart of the same vaccine powder, without alum, mixed with chitosan. Nasal immunization was well tolerated, with fewer symptoms reported than after intramuscular injection. The geometric mean concentrations of MCPspecific immunoglobulin G (IgG) after one nasal immunization were 3.25 g/ml in naïve subjects and 14.4 g/ml in subjects previously immunized parenterally, compared with 4.30 g/ml in naïve subjects immunized intramuscularly. The geometric mean titer of serum bactericidal antibody (SBA) rose 24-fold after two nasal immunizations in naïve subjects and was comparable to parenteral immunization (1,080 versus 1,625). All subjects achieved SBA titers associated with protection after two nasal immunizations: even those with titers of <8 at entry. A single nasal immunization boosted the SBA titer to >128 in 96% of previously immunized subjects, and two immunizations achieved this level in 92% of naive subjects. MCP-specific IgG levels were ϳ70% IgG2 and ϳ20% IgG1 after nasal or intramuscular immunization. Increases in CRM197-specific IgG and diphtheria toxin-neutralizing activity were observed after nasal or intramuscular immunization, with balanced IgG1/IgG2 and higher IgG4. Significant MCP-specific secretory IgA was detected in nasal wash only after nasal immunization and predominantly on the immunized side. Simple nasal insufflation of existing MCP-CRM197 conjugate vaccines in chitosan offers an inexpensive but effective needle-free prime and boost against serogroup C N. meningitidis and diphtheria.

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Section: Discussionsupporting

confidence: 62%

Induction of Protective Serum Meningococcal Bactericidal and Diphtheria-Neutralizing Antibodies and Mucosal Immunoglobulin A in Volunteers by Nasal Insufflations of theNeisseria meningitidisSerogroup C Polysaccharide-CRM197 Conjugate Vaccine Mixed with Chitosan

et al. 2005

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“…PSs are classified as thymus-independent-2 (TI-2) antigens (Ags) because they do not require mature T cells to elicit a humoral response in vivo. These PS Ags are immunogenic in adults but are only poorly or nonimmunogenic in infants and young children who are highly susceptible to infection caused by encapsulated bacteria (28,31,44,65).The response to capsular PS is markedly different from the response to most protein Ags (thymus-dependent [TD] Ags). The Ab response to TI-2 Ag develops late in ontogeny (25,44,50) and in mice utilizes a particular late-developing subset of B cells that is defined by the expression of Lyb5 and other cell markers (39, 60).…”

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confidence: 99%

mentioning

confidence: 99%

Murine Immune Response toNeisseria meningitidisGroup C Capsular Polysaccharide: Analysis of Monoclonal Antibodies Generated in Response to a Thymus-Independent Antigen and a Thymus-Dependent Toxoid Conjugate Vaccine

et al. 2000

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Antibody (Ab) responses to polysaccharides (PSs) such as Neisseria meningitidis group C PS (MCPS) are characterized as being thymus independent (TI) and are restricted with regard to clonotype and isotype expression. PS conjugated to proteins, e.g., MCPS coupled to tetanus toxoid (MCPS-TT), elicits a thymusdependent (TD) response. In order to understand the influence of the form of a vaccine (TI versus TD) on the Ab repertoire, we generated monoclonal antibody (MAb) panels from mice immunized and boosted with MCPS or MCPS-TT in different ways. The panels of MAbs were examined for isotype, fine specificity, affinity, and V H gene family usage. The use of MCPS-TT resulted in a shift in the isotype from immunoglobulin M (IgM) and IgG3 elicited in response to the MCPS to primarily IgG1. This isotype shift was accompanied by a change in the fine specificity of the response to the conjugate compared to that of PS. New fine specificities and increased affinity were observed in response to the TD antigen (Ag). Dot blot and Northern analyses of MCPS MAbs revealed that V H gene family usage is dominated by V H J558, used by 23 of 39 MAbs. V H 3609 was seen in three MAbs of restricted fine specificity. V H Q52, V H 7183, and V H VGAM3-8 were seen in more than one MAb across these panels, while V H 10 and V H X24 were detected only once in response to the TI-2 Ag. All MAbs in the panels utilized kappa light chains, and all functional J genes were expressed.The capsular polysaccharide (PS) constitutes the major virulence factor of many pathogenic bacteria that cause invasive diseases. Antibodies (Abs) against these PSs are protective (27,28). PSs are classified as thymus-independent-2 (TI-2) antigens (Ags) because they do not require mature T cells to elicit a humoral response in vivo. These PS Ags are immunogenic in adults but are only poorly or nonimmunogenic in infants and young children who are highly susceptible to infection caused by encapsulated bacteria (28,31,44,65).The response to capsular PS is markedly different from the response to most protein Ags (thymus-dependent [TD] Ags). The Ab response to TI-2 Ag develops late in ontogeny (25,44,50) and in mice utilizes a particular late-developing subset of B cells that is defined by the expression of Lyb5 and other cell markers (39, 60). TI Ags also generally fail to elicit a memory response or show affinity maturation. In contrast, the ability to respond to a TD Ag is present at birth and results in the formation of memory cells, and the Ab response undergoes subsequent affinity maturation upon reimmunization (61). For TI Ag, immunoglobulin G3 (IgG3) and IgM are the major isotypes expressed in mice, even after secondary immunization (45), whereas for TD Ag, the ratio of IgG to IgM increases after secondary immunization, with IgG1 being the major subclass (52,59,60).The majority of the anti-PS responses are oligoclonal and encoded by a few variable regions of the heavy chain (V H ) gene families (10). The anti-␣(133) dextran Ab, for example, expresses mainly the V H J55...

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“…Data analysis was carried out as above except only MenC CDC 1992 was used as a standard with values previously assigned by Hutchins et al (11).…”

Section: Methodsmentioning

confidence: 99%

“…However, achieving a consensus antibody level can prove difficult, as in the case of Haemophilus influenzae reference serum FDA 1983, in which a variety of techniques were used (8,9,12). Various methods can be used to assign reference sera antibody concentrations, including quantitative precipitation assays (14,19,21), homologous or heterologous enzyme-linked immunosorbent assay (ELISA) formats (10) and the use of myeloma protein standards (11), all methodologies used in the past. The method of cross standardization between different antigens has been reported by Concepcion and Frasch (5), who evaluated previously assigned IgG values in the pneumococcal reference serum 89SF by this method.…”

mentioning

confidence: 99%

Assignment ofNeisseria meningitidisSerogroups A, C, W135, and Y Anticapsular Total Immunoglobulin G (IgG), IgG1, and IgG2 Concentrations to Reference Sera

Joseph

Balmer

Bybel

et al. 2004

Clin Vaccine Immunol

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Meningococcal serogroup-specific immunoglobulin G (IgG), IgG1, and IgG2 concentrations were assigned to three reference sera, CDC 1992, 89-SF, and 96/562, for meningococcal serogroups A, C, Y, and W135 via the method of cross standardization. The sum of the serogroup-specific IgG1 and IgG2 concentrations determined for the four meningococcal serogroups showed good agreement with the serogroup-specific IgG either determined here or as previously represented. Following the assignment of meningococcal serogroup-specific IgG1 and IgG2 concentration to these reference sera, a meningococcal serogroup-specific IgG1 and IgG2 enzymelinked immunosorbent assay protocol was developed. The serogroup A and C specific subclass distribution of a panel of adult sera collected following vaccination with any combination of meningococcal serogroup C conjugate, bivalent, or tetravalent polysaccharide vaccines was determined. For the determination of serogroup W135 and Y specific subclass distribution, an adolescent panel 28 days following a single dose of either tetravalent polysaccharide or conjugate vaccine was used. The sum of the serogroup-specific IgG1 and IgG2 showed strong correlation with the serogroup-specific total IgG determined. The assignment here of IgG1 and IgG2 subclasses to these reference sera will allow more detailed evaluation of meningococcal conjugate and polysaccharide vaccines.

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Elderly Immune Response to a TI‐2 Antigen: Heavy and Light Chain Use and Bactericidal Activity toNeisseria meningitidisSerogroup C Polysaccharide

Cited by 16 publications

References 61 publications

Induction of Protective Serum Meningococcal Bactericidal and Diphtheria-Neutralizing Antibodies and Mucosal Immunoglobulin A in Volunteers by Nasal Insufflations of theNeisseria meningitidisSerogroup C Polysaccharide-CRM197 Conjugate Vaccine Mixed with Chitosan

Induction of Protective Serum Meningococcal Bactericidal and Diphtheria-Neutralizing Antibodies and Mucosal Immunoglobulin A in Volunteers by Nasal Insufflations of theNeisseria meningitidisSerogroup C Polysaccharide-CRM197 Conjugate Vaccine Mixed with Chitosan

Murine Immune Response toNeisseria meningitidisGroup C Capsular Polysaccharide: Analysis of Monoclonal Antibodies Generated in Response to a Thymus-Independent Antigen and a Thymus-Dependent Toxoid Conjugate Vaccine

Assignment ofNeisseria meningitidisSerogroups A, C, W135, and Y Anticapsular Total Immunoglobulin G (IgG), IgG1, and IgG2 Concentrations to Reference Sera

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