Response of 7- to 15-Month-Old Infants to Sequential Immunization With Haemophilus influenzae Type b-CRM197 Conjugate and Polysaccharide Vaccines

Rothstein, Edward; Schiller, Ruth P.; Girone, Joseph A. C.; Hipp, Thomas; Souder, Ronald L.; Bernstein, Henry H.; Madore, Dace V.; Johnson, Cynthia; Smith, David H.

doi:10.1001/archpedi.1991.02160080076024

Cited by 5 publications

(5 citation statements)

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“…For certain types of pneumococcus, there were enhancements of immune response in groups primed with the conjugate vaccines and benefits to the subsequent injection of polysaccharide (31,40). This phenomenon was not obvious in the cases of meningococcal or Haemophilus influenzae type b conjugates, where the best immune response still came from using the conjugate vaccine for the full course of immunization (3,4,6,9,41).…”

Section: Discussionmentioning

confidence: 99%

“…Other reasons for such trials were to explore alternative immunization schedules and formulations. There were several attempts to study the immunological memory induced by polysaccharide on the conjugate, or vice versa (3,4,6,9,31,40,41). For certain types of pneumococcus, there were enhancements of immune response in groups primed with the conjugate vaccines and benefits to the subsequent injection of polysaccharide (31,40).…”

Section: Discussionmentioning

confidence: 99%

“…Priming or boosting effects of polysaccharide on its conjugate vaccine have been observed in infants injected with pneumococcal and meningococcal vaccines (3,4,31,40). There was no consistent conclusion about various types of polysaccharides studied (6,9,31,40,41). Here, we compared the immune response of Vi polysaccharide injected before or after the administration of Vi-DT with the responses of those receiving 2 injections of Vi-DT.…”

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confidence: 99%

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Physical and Chemical Characterization and Immunologic Properties ofSalmonella entericaSerovar Typhi Capsular Polysaccharide-Diphtheria Toxoid Conjugates

Cui

Carbis

et al. 2010

Clin Vaccine Immunol

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Typhoid fever remains a serious public health problem in developing countries, especially among young children. Recent studies showed more than 50% of typhoid cases are in children under 5 years old. Licensed vaccines, such as Salmonella enterica serovar Typhi capsular Vi, did not confer protection against typhoid fever for this age group. Vi conjugate, prepared by binding Vi to Pseudomonas aeruginosa recombinant exoprotein A (rEPA), induces protective levels of antibody at as young as 2 years old. Because of the lack of regulatory precedent for rEPA in licensing vaccines, we employed diphtheria toxoid (DT) as the carrier protein to accommodate accessibility in developing countries. Five lots of Vi-DT conjugates were prepared using adipic acid dihydrazide (ADH) as the linker. All 5 lots showed consistency in their physical and chemical characteristics and final yields. These Vi-DT conjugates elicited levels of IgG anti-Vi in young mice significantly higher than those in mice injected with Vi alone and induced a booster response upon reinjection. This booster effect was absent if the Vi replaced one of the two conjugate injections. Vi-DT was stable under repeated freeze-thaw (20 cycles). We plan to perform clinical evaluation of the safety and immunogenicity of Vi-DT when added to the infant combination vaccines.Typhoid fever, a serious systemic infection caused by Salmonella enterica serovar Typhi, remains a major public health problem in Central Asia, Southeast Asia, Africa, and Latin America (11,52,53). It was estimated that more than 21 million cases of typhoid fever and Ͼ200,000 deaths occurred in 2000 (10). The treatment of patients and management of asymptomatic carriers are becoming more difficult due to the worldwide emergence of multidrug-resistant (MDR) strains (2,15,29,42,43). Vaccination is considered the most promising strategy for the control of typhoid fever in developing countries (11,19,52,53).Typhoid fever in children younger than 5 years old has often been unrecognized due to atypical clinical symptoms, difficulties in the number and volume of blood drawings, and use of less than optimal culture media (35,46). Several studies have shown that the incidence of typhoid fever among children less than 5 years old is similar to that in school age children and young adults (14,27,34,50,51).The 3 licensed typhoid vaccines have limited efficacy, and none are suitable for young children under 5 years old. The use of heat-inactivated whole-cell vaccine was suspended in many countries because of its reactogenicity. The parenteral Vi polysaccharide and the live attenuated oral Ty21a vaccine were introduced in the late 1980s; both vaccines are well accepted and confer moderate protection (50 to 70%) in older children and adults. However, neither vaccine is licensed for routine immunization of infants (52).The Vi capsular polysaccharide is both an essential virulence factor and a protective antigen for S. Typhi (36,38,39). The concentration of serum IgG anti-Vi is correlated with immunity to the pathogen (22...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Physical and Chemical Characterization and Immunologic Properties ofSalmonella entericaSerovar Typhi Capsular Polysaccharide-Diphtheria Toxoid Conjugates

Cui

Carbis

et al. 2010

Clin Vaccine Immunol

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“…Parameters describing resistance due to UK primary course conjugate vaccination (ω HV ( a ), ω LV ) were estimated from clinical trials data [2, 24]. A series of trials conducted in US toddlers reported age-dependent antibody responses and persistence following a single dose of Hib-CRM 197 conjugate (HbOC) [31, 32], the vaccine predominantly used in the catch-up campaign. The estimated duration of low-level antibody persistence after immunization (1/ω LV ) was later subjected to sensitivity analysis.…”

Section: Methodsmentioning

confidence: 99%

“…HbOC, used for catch-up immunization, was highly immunogenic in children aged 12 months and older, with 98-99% achieving post vaccination Hib antibody titres >1 . 0 mg/ml [31,32].…”

Section: Resistantpsusceptiblementioning

confidence: 99%

Understanding the impact of Hib conjugate vaccine on transmission, immunity and disease in the United Kingdom

2007

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A rise in invasive Haemophilus influenzae type b (Hib) infections occurred 8 years after vaccine introduction in the United Kingdom. Aspects of Hib vaccine delivery unique to the United Kingdom have been implicated. The authors developed a fully age-structured deterministic susceptible-infected-resistant-susceptible mathematical model, expressed as a set of partial differential equations, to better understand the causes of declining vaccine effectiveness. We also investigated the consequences of the vaccine's impact on reducing Hib transmission for maintenance of immunity. Our findings emphasized the importance of maintaining high post-immunization antibody titres among age groups at greatest risk of invasive infections. In keeping with UK population-based estimates, low direct efficacy of immunological memory against disease was found, cautioning against over-reliance on evidence of priming alone as a correlate of population protection. The contribution of herd immunity to disease control was reinforced. Possible intervention strategies will be explored in subsequent work.

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

Granoff

Holmes

Osterholm

et al. 1993

Journal of Infectious Diseases

100

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The ability of different Haemophilus influenzae type b conjugate vaccines to induce immunologic memory was compared in 381 infants who were vaccinated with one of three conjugate vaccines beginning at 2 months of age. All infants were vaccinated with unconjugated type b capsular polysaccharide, polyribosylribitol phosphate (PRP), at 12 months. In each group, high antibody responses were detected by 6-9 days after vaccination. One month after receiving PRP, infants primed with PRP conjugated to the outer membrane protein of Neisseria meningitidis or PRP oligomers conjugated to the cross-reactive mutant diphtheria protein, CRM197, had twofold higher total anti-PRP antibody concentrations than did infants primed with PRP conjugated to tetanus toxoid (P < .005). After the conjugate and the PRP boost, notable differences were present among vaccine groups with respect to the magnitude of the IgG anti-PRP antibody concentrations and light chain variable region usage as determined by idiotypic analysis. Thus, each of the conjugate vaccines primed infants for the ability to evoke memory antibody responses to PRP, but qualitative and quantitative differences in priming induced by different vaccines may affect their ability to confer protection against disease.

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Response of 7- to 15-Month-Old Infants to Sequential Immunization With Haemophilus influenzae Type b-CRM197 Conjugate and Polysaccharide Vaccines

Cited by 5 publications

References 4 publications

Physical and Chemical Characterization and Immunologic Properties ofSalmonella entericaSerovar Typhi Capsular Polysaccharide-Diphtheria Toxoid Conjugates

Physical and Chemical Characterization and Immunologic Properties ofSalmonella entericaSerovar Typhi Capsular Polysaccharide-Diphtheria Toxoid Conjugates

Understanding the impact of Hib conjugate vaccine on transmission, immunity and disease in the United Kingdom

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

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