Induction of Immunologic Memory in Infants Primed with Haemophilus influenzae Type b Conjugate Vaccines

Granoff, Dan M.; Holmes, Scott A.; Osterholm, Michael T.; McHugh, Joseph E.; Lucas, Alexander H.; Anderson, Edwin L.; Belshe, Robert B.; Jacobs, Jean L.; Medley, Francinne; Murphy, T. V.

doi:10.1093/infdis/168.3.663

Cited by 100 publications

(35 citation statements)

References 30 publications

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“…These memory B cells can be subsequently triggered by intact MenC to differentiate into plasma cells, similar to our data, although in this case requiring contact-dependent (in part through CD40) but noncognate help from bystander CD4 + T cells specific for MenC proteins (46). Meningococcal, Haemophilus influenzae type b, and pneumococcal conjugate vaccines also induce memory B cells that can be subsequently triggered for PS-specific IgG responses by the respective unconjugated PS, implying that only memory B cells, and not T cells, play a key role in these IgG responses (47)(48)(49)(50)(51)(52)(53). It has been proposed that natural priming of humans by exposure to PSencapsulated bacteria may induce memory B cells that can be subsequently triggered in a TI manner, because vaccination of adults with capsular PS vaccines shows features of a secondary Ab (i.e., hypermutated IgG) (54-58).…”

Section: Discussionsupporting

confidence: 87%

Distinct Mechanisms Underlie Boosted Polysaccharide-Specific IgG Responses Following Secondary Challenge with Intact Gram-Negative versus Gram-Positive Extracellular Bacteria

Kar

Arjunaraja

Akkoyunlu

et al. 2016

The Journal of Immunology

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Priming of mice with intact, heat-killed cells of Gram-negative Neisseria meningitidis, capsular serogroup C (MenC) or Gram-positive group B Streptococcus, capsular type III (GBS-III) bacteria resulted in augmented serum polysaccharide (PS)-specific IgG titers following booster immunization. Induction of memory required CD4+ T cells during primary immunization. We determined whether PS-specific memory for IgG production was contained within the B cell and/or T cell populations, and whether augmented IgG responses following booster immunization were also dependent on CD4+ T cells. Adoptive transfer of purified B cells from MenC- or GBS-III–primed, but not naive mice resulted in augmented PS-specific IgG responses following booster immunization. Similar responses were observed when cotransferred CD4+ T cells were from primed or naive mice. Similarly, primary immunization with unencapsulated MenC or GBS-III, to potentially prime CD4+ T cells, failed to enhance PS-specific IgG responses following booster immunization with their encapsulated isogenic partners. Furthermore, in contrast to GBS-III, depletion of CD4+ T cells during secondary immunization with MenC or another Gram-negative bacteria, Acinetobacter baumannii, did not inhibit augmented PS-specific IgG booster responses of mice primed with heat-killed cells. Also, in contrast with GBS-III, booster immunization of MenC-primed mice with isolated MenC-PS, a TI Ag, or a conjugate of MenC-PS and tetanus toxoid elicited an augmented PS-specific IgG response similar to booster immunization with intact MenC. These data demonstrate that memory for augmented PS-specific IgG booster responses to Gram-negative and Gram-positive bacteria is contained solely within the B cell compartment, with a differential requirement for CD4+ T cells for augmented IgG responses following booster immunization.

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Section: Discussionsupporting

confidence: 87%

Distinct Mechanisms Underlie Boosted Polysaccharide-Specific IgG Responses Following Secondary Challenge with Intact Gram-Negative versus Gram-Positive Extracellular Bacteria

Kar

Arjunaraja

Akkoyunlu

et al. 2016

The Journal of Immunology

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“…This is supported by studies of Hib conjugate vaccines, which have shown similar efficacy of the PRP-OMPC vaccine (51), despite the lower immunogenicity of the vaccine and the lower mean avidity of antibodies compared to the other Hib conjugate vaccines (12,22,52). In the FinOM Vaccine Efficacy Trial, the aggregate vaccine efficacy of serotypes contained in the vaccine, and also the serotype-specific efficacies against AOM of both PCVs, were evaluated in parallel (17,32).…”

Section: Discussionmentioning

confidence: 92%

“…In addition, markers associated with the development of B-cell memory should be considered. Demonstration of B-cell memory has largely been based on the kinetics of antibody development and a rapid and strong antibody response to a dose of plain polysaccharide vaccine after priming with a conjugate vaccine (2,14,22,29,43,45). It has also been suggested that B-cell memory can be demonstrated by showing avidity maturation of the antibodies (3,20,28,36,50).…”

mentioning

confidence: 99%

Kinetics and Avidity of Antibodies Evoked by Heptavalent Pneumococcal Conjugate Vaccines PncCRM and PncOMPC in the Finnish Otitis Media Vaccine Trial

et al. 2005

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The licensure of new pneumococcal conjugate vaccines (PCVs) relies on immunogenicity data. When defining correlates of protection, vaccine efficacy data must be included. In the FinOM Vaccine Efficacy Trial, the PncOMPC vaccine showed an efficacy profile similar to that of the licensed PncCRM vaccine despite different antibody responses after primary and booster vaccinations. We determined antibody kinetics and avidities in a subgroup of infants participating in the FinOM trial. A total of 166 infants in three vaccine groups were immunized at 2, 4, 6, and 12 months of age with 7-valent PCV, PncCRM or PncOMPC, or hepatitis B vaccine. Concentrations of serum immunoglobulin G (IgG) against pneumococcal capsular polysaccharides were determined at 2, 4, 6, 7, 12, 13, and 24 months of age, and the avidity index (AI) to serotypes 6B, 19F, and 23F were determined at 7, 12, 13, and 24 months of age by enzyme immunoassay. Both PCVs were highly immunogenic, but they demonstrated different kinetics of antibody response; the concentration of IgG against serotypes 6B, 19F, and 23F declined faster after the third and fourth doses of vaccine in the PncCRM group than in the PncOMPC group. For both PCVs, the mean AI of anti-6B and -23F, but not of anti-19F, increased during the follow-up, which is in line with serotype-specific protection in the FinOM trial. Our data suggest that the kinetics and avidities of antibodies should be considered, in addition to antibody responses, when defining correlates of protection.

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“…By chromogenic Limulus amebocyte lysate assay (Microbiological Associates, Gaithersburg, MD), these reagents contained the following amounts of endotoxin: E. coli LPS =6711. 4 -ethanol precipitation as described [48]. LPS fatty acids (lipid A) was obtained by hydrolysis of LPS in 1% SDS at pH 4.5 [49].…”

Section: Reagentsmentioning

confidence: 99%

“…The most substantive advance in vaccines against this class of pathogens was the development of H. influenzae type b capsular polysaccharides (PRP) vaccines, which has lead to a dramatic decrease in the incidence of disease due to this organism. Each of the four PRP conjugate vaccines licensed in the United States has been inferred to induce T cell-dependent antibody production, although the dependence of these vaccines on cognate T cell help has not been formally tested [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Carrier-mediated enhancement of cognate T cell help: the basis for enhanced immunogenicity of meningococcal outer membrane protein polysaccharide conjugate vaccine

Pérez-Melgosa¹,

Ochs²,

Linsley³

et al. 2001

Eur. J. Immunol.

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Induction of Immunologic Memory in Infants Primed with Haemophilus influenzae Type b Conjugate Vaccines

Cited by 100 publications

References 30 publications

Distinct Mechanisms Underlie Boosted Polysaccharide-Specific IgG Responses Following Secondary Challenge with Intact Gram-Negative versus Gram-Positive Extracellular Bacteria

Distinct Mechanisms Underlie Boosted Polysaccharide-Specific IgG Responses Following Secondary Challenge with Intact Gram-Negative versus Gram-Positive Extracellular Bacteria

Kinetics and Avidity of Antibodies Evoked by Heptavalent Pneumococcal Conjugate Vaccines PncCRM and PncOMPC in the Finnish Otitis Media Vaccine Trial

Carrier-mediated enhancement of cognate T cell help: the basis for enhanced immunogenicity of meningococcal outer membrane protein polysaccharide conjugate vaccine

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