Heteroimmunization to the capsular polysaccharide of Haemophilus influenzae type b induced by enteric cross-reacting bacteria

Handzel, Zeev T.; Argaman, M.; Parke, J. C.; Schneerson, Rachel; Robbins, John B.

doi:10.1128/iai.11.5.1045-1052.1975

Cited by 29 publications

(14 citation statements)

References 26 publications

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“…In contrast, compared with formula-fed counterparts, Australian breastfed infants had lower anti-HibPS concentrations both before and after completed immunization with Hib conjugate vaccine (24). Several species of commensal bacteria in the gut and respiratory tract display antigens that cross-react with Hib (25). We speculate that the greater anti-HibPS concentrations in infants BF < 6 months originate in a more diverse microbiota with consequently earlier stimulation of the developing immune system.…”

Section: Probiotics Infections and Vaccine Responsementioning

confidence: 80%

Effects of feeding probiotics during weaning on infections and antibody responses to diphtheria, tetanus and Hib vaccines

West

Gothefors

Granström

et al. 2008

Pediatric Allergy Immunology

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Microbial exposure is necessary for the development of normal immune function, which has driven the idea of using probiotics for treatment and prevention of immune-mediated diseases in infancy and childhood. Mounting evidence indicates that probiotics have immunomodulatory effects. However, the mechanisms are still poorly understood. Specific antibody response is a valuable proxy for immune system maturation status in infancy. We aimed at determining the impact of Lactobacillus F19 (LF19) during weaning on infections and IgG antibody responses to routine vaccines. In a double-blind, placebo-controlled randomized intervention trial, infants were fed cereals with (n = 89) or without LF19 (n = 90) from 4 to 13 months of age. Infants were immunized with DTaP (diphtheria and tetanus toxoid and acellular pertussis), polio and Hib-conjugate vaccines at (3), 5(1/2) and 12 months of age. We assessed the number of days with infections, antibiotic prescriptions and antibody concentrations to Hib capsular polysaccharide (HibPS), diphtheria toxin (D) and tetanus toxoid (T) before and after the second and third doses. Days with infectious symptoms did not differ between the groups. Days with antibiotic prescriptions were fewer in the LF19 group (p = 0.044). LF19 enhanced anti-D concentrations when adjusting for breastfeeding duration and colonization with LF19 (p = 0.024). There was an interaction of the intervention and colonization with LF19 on anti-T concentrations during the course of vaccination (p = 0.035). The anti-HibPS concentrations were higher after the first and second dose of Hib vaccine in infants breastfed <6 months compared with those breastfed > or =6 months (p < 0.05), with no effect by LF19. In conclusion, feeding LF19 did not prevent infections, but increased the capacity to raise immune responses to protein antigens, with more pronounced effects in infants breastfed <6 months.

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Section: Probiotics Infections and Vaccine Responsementioning

confidence: 80%

Effects of feeding probiotics during weaning on infections and antibody responses to diphtheria, tetanus and Hib vaccines

West

Gothefors

Granström

et al. 2008

Pediatric Allergy Immunology

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“…(c) Reinjection of HIB-Ps-protein conjugates induced an increase in both the number of responders and in the total level of anti-type b Ab (booster effect) (57-59). (d) Carrier priming, induced by the BSA and AH-BSA derivatives, resulted in an enhanced serum anti-type b antibody response to initial immunization with the conjugate (59)(60)(61)(62). Further experiments to study the cellular basis for the enhanced immungenicity of the HIB Ps-protein conjugates and the molecular characteristics of the serum antibodies are planned (60,61).…”

Section: Discussionmentioning

confidence: 99%

Preparation, characterization, and immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugates.

Schneerson¹,

Barrera²,

Sutton³

et al. 1980

The Journal of Experimental Medicine

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591

283

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A method is presented for covalently bonding Haemophilus influenzae type b capsular polysaccharide (HIB Ps) to several proteins. The method is efficient and relies upon the use of adipic dihydrazide as a spacer between the capsular polysaccharide and the carrier protein. In contrast to the poor immunogenicity of the purified HIB Ps in mice and rabbits, the HIB Ps-protein conjugates induced serum anti-type b antibodies having bactericidal activity at levels shown to be protective in humans when low doses were injected subcutaneously in a saline solution. The antibody response in mice was related to the dose of the conjugates, increased with the number of injections, and could be primed by the previous injection of the carrier protein. The HIB Ps-protein conjugates were immunogenic in three different mouse strains. The importance of the carrier molecule for the enhanced immunogenicity of the HIB Ps-protein conjugates was shown by the failure of HIB Ps hybrids prepared with either the homologous polysaccharide or pneumococcus type 3 polysaccharide to induce antibodie in mice. Rabbits injected with the HIB Ps-protein conjugates emulsified in Freund's adjuvant produced high levels of serum anti-type b antibodies which induced a bactericidal effect upon H. influenzae type b organisms. It is proposed that the HIB Ps component of the polysaccharide protein conjugates has been converted to a thymic-dependent immunogen. This method may be used to prepare protein-polysaccharide conjugates with HIB Ps and other polysaccharides to be considered for human use.

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“…The latter hypothesis disregards any protective value of serum IgA and is not supported by results obtained in the infant rat model. Thus, studies with H. injiuenzue type b infection have shown that colonization of the gut with crossreactive bacteria (E. coli K 100) protects against such invasive infection (43). According to our 330 hypothesis that IgAl protease is a central factor, rats do not become susceptible as a result of preexisting IgA antibodies, but rather protected, because their IgA is not cleavable by IgA1 proteases.…”

Section: Hypotheticul Model For Puthogenesis Qf Invusive In Fret Ionsmentioning

confidence: 95%

Biological significance of IgA1 proteases in bacterial colonization and pathogenesis: critical evaluation of experimental evidence

Kilian¹,

Reinholdt²,

Lomholt³

et al. 1996

Apmis

262

210

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IgA1 protease activity, which allows bacteria to cleave human IgA1 in the hinge region, represents a striking example of convergent evolution of a specific property in bacteria. Although it has been known since 1979 that IgA1 protease is produced by the three leading causes of bacterial meningitis in addition to important urogenital pathogens and some members of the oropharyngeal flora, the exact role of this enzyme in bacterial pathogenesis is still incompletely understood owing to lack of a satisfactory animal model. Cleavage of IgA1 by these post‐proline endopeptidases efficiently separates the monomeric antigen‐binding fragments from the secondary effector functions of the IgA1 antibody molecule. Several in vivo and in vitro observations indicate that the enzymes are important for the ability of bacteria to colonize mucosal membranes in the presence of S‐IgA antibodies. Furthermore, the extensive cleavage of IgA sometimes observed in vivo, suggests that IgA1 protease activity results in a local functional IgA deficiency that may facilitate colonization of other microorganisms and the penetration of potential allergens. It has been hypothesized that IgA1 protease activity of Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae, under special immunological circumstances, allows these bacteria to take advantage of specific IgA1 antibodies in a strategy to evade other immune factors of the human body. The decisive factor is the balance between IgA antibodies against surface antigens of the respective bacteria and their IgA1 protease. Recent studies have shown that serine‐type IgA1 proteases of H. influenzae, meningococci, and gonococci belong to a family of proteins used by a diverse group of Gramnegative bacteria for colonization and invasion.

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Heteroimmunization to the capsular polysaccharide of Haemophilus influenzae type b induced by enteric cross-reacting bacteria

Cited by 29 publications

References 26 publications

Effects of feeding probiotics during weaning on infections and antibody responses to diphtheria, tetanus and Hib vaccines

Effects of feeding probiotics during weaning on infections and antibody responses to diphtheria, tetanus and Hib vaccines

Preparation, characterization, and immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugates.

Biological significance of IgA1 proteases in bacterial colonization and pathogenesis: critical evaluation of experimental evidence

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