Outer Membrane Protein Conjugate Research Articles

Experience with the prevention of invasive Haemophilus influenzae type b disease by vaccination in Alaska: The impact of persistent oropharyngeal carriage

Objectives: To report the epidemiology of invasive Haemophilus influenzae type b (Hib) disease in high-risk Alaska Native infants before and after universal infant Hib vaccination and evaluate an increase in invasive Hib disease in 1996 after changing Hib vaccine type. Study design: Statewide laboratory surveillance for invasive Hib disease has been conducted since 1980. Three cross-sectional Hib carriage studies were conducted in 1997 and 1998. Results: The invasive Hib disease rate in Alaska Natives decreased from 332 cases per 100,000 children <5 years old in 1980-1991 to 17:100,000 in 1992-1995 but increased primarily in rural areas to 57.9:100,000 after a switch in Hib vaccine types. Carriage studies in 5 rural Alaska Native villages showed oropharyngeal Hib carriage as high as 9.3% in children aged 1 to 5 years; in contrast, carriage in urban Alaska Native children was <1%. Conclusions: Although Hib disease has decreased in Alaska, the rate of Hib disease and carriage in rural Alaska Natives did not decrease to the same extent as in non-Natives and urban Alaska Natives. Use of polyribosylribitol phosphate–outer-membrane protein conjugate vaccine for the first vaccine dose is critical to disease control in this population with continued transmission in infants <6 months of age. The ability to eliminate Hib carriage and disease may be affected by population characteristics, vaccination coverage, and Hib vaccine type used. This may pose a challenge to global elimination of Hib. (J Pediatr 2000;137:313-20)

Differing serologic responses to an Haemophilus influenzae type b polysaccharide– Neisseria meningitidis outer membrane protein conjugate (PRP–OMPC) vaccine in Australian Aboriginal and Caucasian infants — implications for disease epidemiology

This study compared Hib antibody responses to a single lot of PRP–OMPC vaccine given at 2, 4 and 12 months to 57 Aboriginal infants in rural areas of the Northern Territory and 56 Caucasian infants in Sydney, Australia. The Aboriginal infants had lower levels of antibody in cord blood ( P>0.05), which were significantly lower ( P<0.02) by 2 months of age. Antibody responses to one or two doses of vaccine, measured at 4 and 12 months of age, were similar but the geometric mean titre following the booster dose in Aboriginal infants was significantly lower (1.98 vs 6.04 mcg/ml, P=0.002). Low preimmunisation antibody is consistent with the early onset of Hib disease in Aboriginal infants before immunisation. Lower responses to boosting could correlate with persistence of Hib colonisation in indigenous populations.

Pneumococcal conjugate vaccination in adults: circulating antibody secreting cell response and humoral antibody responses in saliva and in serum

The results from our previous study showed IgA dominated ASC responses to pneumococcal polysaccharide vaccine and to pneumococcal polysaccharide meningococcal outer membrane protein conjugate vaccine (PncOMPC) in adult volunteers. The results indicated that a high IgA ASC response is a useful indicator of a secretory IgA response in saliva. We believe that the mucosal immune responses is potentially an important characteristic of the pneumococcal vaccines and should thus be measured when the new pneumococcal conjugate vaccines are evaluated. In the present study, we studied two new tetravalent pneumococcal conjugate vaccines: the diphtheria toxoid and tetanus toxoid conjugates. In contrast to PncOMPC, these conjugates induced higher responses than the polysaccharide vaccine. Furthermore, the different structure of the two conjugate vaccines might affect the nature of the response. Thus a different vaccine may be optimal for induction of a mucosal response than is of systemic responses.

Postlicensure effectiveness of the Haemophilus influenzae type b polysaccharide- Neisseria meningitidis outer-membrane protein complex conjugate vaccine among Navajo children

The incidence of invasive Haemophilus influenzae type b (Hib) infection has decreased significantly among Navajo children since the licensure of Hib conjugate vaccines, even though two lots of Hib (polyribosylribitol phosphate)-meningococcal B outer-membrane protein conjugate vaccine (PRP-OMP) widely used among the Navajo were later found to be of low immunogenicity. We measured the effectiveness of all Hib conjugate vaccines combined, PRP-OMP alone, and the PRP-OMP lots with lower-than-expected immunogenicity among Navajo infants and children. This was a matched case-control study using active, laboratory-based surveillance for the ascertainment of Navajo children 21/2 to 59 months of age with invasive Hib infection; 45 patients with infection and 180 control subjects were enrolled. The effectiveness of one, two, and three doses, respectively, of all Hib conjugate vaccines combined was 96% (95% confidence interval [CI] 65%, 99%), 99% (95% CI, 69%, 100%), and 99% (95% CI, –57%, 100%). The effectiveness of one or more doses of PRP-OMP was 95% (95% CI, 66%, 99%). The effectiveness of a single dose of the lots of lower-than- expected immunogenicity was 89% (95% CI, –8%, 99%). The Hib conjugate vaccine coverage increased from 49% during 1991 to 94% during 1992; no control subjects younger than 18 months of age were enrolled during 1993. The occurrence of invasive Hib infections in this population after licensure of Hib conjugate vaccines was the result of gradual vaccine uptake, not poor vaccine effectiveness. The use of PRP-OMP has been highly effective despite concerns about the immunogenicity of several lots. (J P EDIATR 1994;125:571-6)

Letters to the Editor

Journal of Paediatrics and Child HealthVolume 29, Issue 6 p. 481-484 Free Access Letters to the Editor First published: December 1993 https://doi.org/10.1111/j.1440-1754.1993.tb03027.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat REFERENCES 1 Beauchamp G., Kosmorsky G. Learning disabilities: Update comment on the visual system. Pediatr. Clin. North Am. 1987; 34: 1439– 45. 2 Helveston E. M., Ellis F. D., Estes R. et al. Visual function and academic performance. Am. J. Ophthalmol. 1985; 99: 346– 55. 3 American Academy of Pediatrics, Committee on Children with Disabilities, American Association for Pediatric Ophthalmology and Strabismus and American Academy of Ophthalmology. Policy statement on learning disabilities, dyslexia and vision. Pediatrics 1992; 90: 124– 6. 4 Health Care Committee, NH&MRC. Learning Difficulties in Children and Adolescents. NH&MRC, May 1990. 5 The Royal Australian College of Ophthalmologists and The Australian College of Paediatrics. Joint Policy Statement on Learning Disabilities, Dyslexia and Vision. October 1990. 1 Spinola S. M., Sheaffer C. I., Philbrick K. B., Gilligan P. H. Antigenuria after Haemophilus influenzae type b polysaccharide immunization: A prospective study. J. Pediatr. 1986; 109: 835– 7. 2 Sood S. K., Ballanco G. A., Mather F. J., Pramberg J. C., Daum R. S. Distribution and excretion of capsular antigen after immunization with Haemophilus influenzae type b polysaccharide-Ne/sser/a meningitidis outer membrane protein conjugate vaccine. J. Infect. Dis. 1990; 161: 574– 7. 3 Rothstein E. P., Madore D. V., Girone J. A. C. et al. Comparison of antigenuria after immunization with three Haemophilus influenzae type b conjugate vaccines. Pediatr. Infect. Dis. J. 1991; 10: 311– 14. 4 Ingram D. L., Paerson A. W., Occhiuti A. R. Detection of bacterial antigens in body fluids with the Wellcogen Haemophilus influenzae b, Streptococcus pneumoniae and Neisseria meningitidis (ACYW135) latex agglutination tests. J. Clin. Microbiol. 1983; 18: 1119– 21. 5 Lampe R. M., Chottipitayasunondh T., Sunakorn P. Detection of bacterial antigen in pleural fluid by counterimmuno-electrophoresis. J. Pediatr. 1976; 88: 557– 60. 6 Murphy T. V., Clements J. F., Granoff D. M. Concentration of Haemophilus influenzae type b (HIB) polysaccharide (PRP) in urine of healthy HIB carriers and patients with diseases as measured by ELISA. Pediatr. Res. 1989; 25 (Part 2): 185A. 1 Butler K. M., Baker C. J. Candida: An increasingly important pathogen in the nursery. Pediatr. Clin. North Am. 1988; 35: 543– 63. 2 Ho N. K. Systemic candidiasis in premature infants. Aust. Paediatr. J. 1984; 20: 127– 30. 3 Stuck K. J., Silver T. M., Jaffe M. H., Bowerman R. A. Sonographic demonstration of renal fungal balls. Radiology 1981; 142: 473– 4. 4 Hufnagle K. G., Khan S. N., Penn D., Cacciarelli A., Williams P. Renal calcifications: A complication of long term frusemide therapy. Pediatrics 1982; 70: 360– 3. 5 Cramer B. C., Ozere R., Andrews W. Renal stone following medical treatment of renal candidiasis. Pediatr. Radiol. 1990; 21: 43– 4. 6 Short A., Cooke R. W. I. The incidence of renal calcification in preterm infants. Arch. Dis. Child. 1991; 66: 412– 17. Citing Literature Volume29, Issue6December 1993Pages 481-484 ReferencesRelatedInformation

Immune Response to Hib Conjugate Vaccine-Reply

In Reply.—Dr Sullivan raises two important considerations when evaluating vaccines in children, immunogenicity and efficacy, ie, against invasiveHaemophilus influenzaetype b disease. Our data demonstrating an inverse relationship of immunogenicity andHaemophilus influenzaetype b capsular polysaccharide—Neisseria meningitidisgroup B outer membrane protein conjugate vaccine (PRP-NOMP) dosage after a second dose of PRP-NOMP cannot directly address the issue of efficacy. We agree that if we were to assume that children achieving anti-PRP antibody levels greater than 1.0 mg/L were protected againstH influenzaetype b disease, our finding of anti-PRP geometric mean titers of 7.3 mg/L after the second dose of PRP-NOMP in the 30-μg PRP dosage may not be of clinical significance (as stated in our article) because almost all the children achieved anti-PRP antibody levels greater than 1.0 mg/L. The suggestion that protection in relation to anti-PRP antibody concentration can be better assessed by comparing age

Duration of serum anticapsular antibody after a two-dose regimen of a Haemophilus influenzae type b polysaccharide- Neisseria meningitidis outer membrane protein conjugate vaccine and anamnestic response after a third dose

Duration of serum anticapsular antibody after a two-dose regimen of a Haemophilus influenzae type b polysaccharide- Neisseria meningitidis outer membrane protein conjugate vaccine and anamnestic response after a third dose

Dose-Related Immunogenicity of Haemophilus influenzae Type b Capsular Polysaccharide—Neisseria meningitidis Outer Membrane Protein Conjugate Vaccine

We studied the immunologic responsiveness to Haemophilus influenzae type b capsular polysaccharide-Neisseria meningitidis group b outer membrane protein conjugate vaccine (PRP-NOMP) in children 2 to 42 months of age with vaccine dosages containing 7.5, 15, or 30 micrograms of PRP. Overall, PRP-NOMP was highly immunogenic. Geometric mean titers of anti-PRP antibody increased from 0.09 to 3.3 mg/L and 6.6 mg/L following each dose of vaccine, respectively, in the 2- to 18-month age group. Similarly, anti-PRP antibody geometric mean titers increased from 0.12 to 5.9 mg/L in the older than 18-month age group. However, we noted an apparent inverse relationship between vaccine dosages and immune responses following two doses of PRP-NOMP in 2- to 18-month-old children. Anti-PRP antibody geometric mean titers were 12.0, 6.9, and 3.5 mg/L, respectively, after the second dose of vaccine containing 7.5, 15, or 30 micrograms of PRP. Additional studies are needed to understand the mechanisms responsible for this inverse relationship and also to determine the optimal dosage of PRP-NOMP for young children.

Immunogenicity and Reactogenicity of Haemophilus influenzae Type b – Meningococcus Group B Outer Membrane Protein Conjugate Vaccine in Children 2–60 Months of Age

Haemophilus influenzae b - Neisseria meningitidis group B outer membrane protein conjugate vaccine (Hib-OMP) was given to 571 children 2-60 months of age. Two doses of Hib-OMP were given, 2 months apart, to 2-11 month old infants, and a single dose to children 12-60 month old. Sera were obtained from a subset of vaccinees at each immunization, and at follow-up 1 month and 1 year after immunization. Geometric mean antibody concentration (micrograms/ml) before and after full immunization were respectively 0.111 and 3.549 for 2-3 month old, 0.108 and 5.048 for 4-5 month old, 0.082 and 6.933 for 6-11 month old; they were 0.103 and 3.500 for 12-17 month old, 0.167 and 7.791 for 18-23 month old and 0.243 and 12.781 for children greater than or equal to 24 months. Detectable antibody (greater than or equal to 0.125 micrograms/ml) failed to develop in 2/399 (0.5%) after primary immunization, and 12/252 (4.8%) lost detectable antibody 1 year later. Six of these 12 infants were less than 12 month old. The vaccine was immunogenic as early as 3-5 months of age. The need for booster immunization needs to be assessed.

Serologic Responses to an Haemophilus influenzae Type b Polysaccharide-Neisseria meningitidis Outer Membrane Protein Conjugate Vaccine in Very Young Gambian Infants

Recent studies in the United States and Europe have shown that Haemophilus influenzae type b polysaccharide-protein conjugate vaccines can induce protective antibody levels in young infants, but it was not clear that this would be the case in African infants, to whom H influenzae vaccines must be given at a very early age to prevent disease caused by H influenzae. Therefore, antibody responses to an H influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine were measured in very young Gambian infants. In the first group (n = 85), to whom the vaccine was given at the ages of 1 and 3 months, the geometric mean antibody level rose from a prevaccination level of 0.23 microgram/mL to a postvaccination level of 1.27 micrograms/mL, and in the second group (n = 56), vaccinated at the ages of 2 and 4 months, the prevaccination level of 0.16 microgram/mL rose to a postvaccination level of 1.59 micrograms/mL. These two final postvaccination levels did not differ significantly, and interpolation suggests that similar antibody levels were present in both groups of infants at the age of 3 months. This is the age by which protection would need to be achieved to protect against H influenzae meningitis in The Gambia and in other countries where the infection has similar epidemiologic characteristics. No significant side effects of vaccination were noted.

Disease Caused by Haemophilus influenzae Type b in the Immediate Period After Homologous Immunization: Immunologic Investigation

Several Haemophilus influenzae type b vaccines have been licensed and recommended for administration to children in the United States. These vaccines have consisted of purified polyribosylribitol-phosphate (PRP), the capsular polysaccharide of H influenzae type b, alone or covalently bound to one of several carrier proteins. Two of these saccharide-protein conjugate vaccines are now licensed, a polysaccharide-diphtheria toxoid conjugate (PRP-D) and an oligosaccharide-mutant diphtheria toxin conjugate (HbOC). Two others, a polysaccharide-Neisseria meningitidis outer membrane protein conjugate (PRP-OMPC) and a polysaccharide-tetanus toxoid conjugate (PRP-T), are currently in clinical trials. One concern with the use of PRP vaccine was the suggestion that the incidence of invasive disease caused by H influenzae type b in the immediate period after immunization might be increased; this idea was supported by evidence from several sources. In a case-control study of the efficacy of PRP vaccine, Black et al found that 4 children were hospitalized for invasive disease within 1 week of immunization, a rate of invasive disease 6.4 times greater (95% confidence interval [CI], 2.1 to 19.2) than the background rate in unvaccinated children. In Minnesota, the relative risk for invasive disease in the first week after immunization was 6.2 (95% CI, 0.6 to 45.9), and the results of a study conducted by the Centers for Disease Control in six areas of the United States revealed a 1.8-fold (95% CI, 0.3 to 10.2) increase in the occurrence of invasive disease caused by H influenzae type b in the first week after immunization.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunologic priming to capsular polysaccharide in infants immunized with Haemophilus influenzae type b polysaccharide— Neisseria meningitidis outer membrane protein conjugate vaccine

Thirty children vaccinated at 2 to 17 months of age with Haemophilus influenzae type b polysaccharide linked to a partially purified 40,000 dalton outer membrane protein of Neisseria meningitidis were revaccinated 10 to 14 months later with conventional H. influenzae type b polysaccharide vaccine. The geometric mean anti-type b antibody concentration before reimmunization was 0.68 micrograms/mL, and rose to 31 micrograms/mL in sera obtained 1 month later. The mean level after immunization was not significantly different than that in sera from 12 adults immunized with type b polysaccharide vaccine (51 micrograms/mL, P = 0.3), and was 10-fold higher than that of 13 control children immunized with type b polysaccharide for the first time (2.7 micrograms/mL, P less than 0.001). The IgG responses of the children first given conjugate vaccine and then conventional type b polysaccharide vaccine were of a similar magnitude as those in the immunized adults. Further, the children maintained high levels of serum antibody 6 to 8 months later. Ten other children vaccinated in infancy with conjugate vaccine, and again with conjugate vaccine 10 to 15 months later, showed similar antibody responses to those of the group given conjugate vaccine in infancy, and booster with conventional polysaccharide vaccine. Thus vaccination with H. influenzae type b polysaccharide-outer membrane protein conjugate vaccine primes the immune system to an IgG memory antibody response to either type b polysaccharide or conjugate vaccine. Post-booster sera from all children tested showed high titers of functional activity in a complement-mediated bactericidal assay. These data suggest that protection of most infants from type b Haemophilus disease may be achieved by a combination of immunization at 2 to 4 months of age with this conjugate vaccine, and reimmunization 1 year later with conjugate or conventional type b polysaccharide vaccine.