Original Article
The Efficacy in Navajo Infants of a Conjugate Vaccine Consisting of Haemophilus influenzae Type b Polysaccharide and Neisseria meningitidis Outer-Membrane Protein Complex
N Engl J Med 1991; 324:1767-1772June 20, 1991
- Abstract
Background and Methods.
Several conjugate vaccines against Haemophilus influenzae type b have been developed in the search for one that induces protection even in young infants. We evaluated the safety and efficacy of a conjugate vaccine that links the H. influenzae type b capsular polysaccharide to the outer-membrane protein complex (OMPC) of Neisseria meningitidis serogroup B. We conducted a double-blind, placebo-controlled trial in Navajo infants, who are at high risk for systemic infections caused by H. influenzae type b. The infants were randomly assigned to receive the first dose of vaccine or placebo at 42 to 90 days of age and the second at 70 to 146 days of age.
Results.
Of the infants in the trial, 2588 were assigned to receive the vaccine and 2602 to receive placebo. The mean follow-up was 269 days in the vaccine group and 267 days in the placebo group. Before the age of 18 months, there was 1 systemic H. influenzae type b infection in the vaccine group, as compared with 22 in the placebo group (P<0.001; point estimate of efficacy, 95 percent; 95 percent confidence interval, 72 to 99 percent). Of the 22 H. influenzae type b infections in the placebo group, 13 were meningitis. Among the children who received both doses, there was 1 H. influenzae type b infection in the vaccine group (n = 2056) and 14 in the placebo group (n = 2105) (P<0.001; point estimate of efficacy, 93 percent; 95 percent confidence interval, 53 to 98 percent). The single infection in the vaccine group occurred at 15 1/2 months of age in an infant with osteomyelitis. Between the first and second doses there were no H. influenzae type b infections in the vaccine group and eight in the placebo group (P<0.005; point estimate of efficacy, 100 percent; 95 percent confidence interval, 41 to 100 percent).
Conclusions.
The H. influenzae type b OMPC vaccine, administered at 2 and 4 months of age, is safe and induces a high rate of protection against invasive disease caused by H. influenzae type b in infants under the age of 18 months. Protection begins after the first dose. (N Engl J Med 1991;324:1767–72.)
Media in This Article
Table 1
Selected Characteristics of the Infants Who Received at Least One Dose of H. influenzae Type b OMPC Vaccine or Placebo.*Table 2
Antibody Responses in Infants Vaccinated with H. influenzae Type b OMPC Vaccine or Placebo.*Article Activity
- Article
HAEMOPHILUS INFLUENZAE type b is the leading cause of meningitis and other serious infections in children.1 2 3 The attack rates of this disease among certain Native American populations, such as Alaskan Eskimos, Navajos, and Apaches, are 5 to 10 times higher than those in the general U.S. population.4 5 6 Moreover, approximately 40 percent of the cases in these populations occur before the age of six months.
Recently, an H. influenzae conjugate vaccine was produced by covalently linking H. influenzae type b capsular polysaccharide to portions of the outer-membrane protein complex (OMPC) of Neisseria meningitidis serogroup B7 (PedvaxHIB, Merck Sharp and Dohme Research Laboratories). This vaccine has been shown to be immunogenic in Navajo, Apache, and white infants after a single dose at six to eight weeks of age.8 9 10 On the basis of the results of immunogenicity studies, we conducted a double-blind, placebo-controlled trial among Navajo infants to evaluate the safety and efficacy of the H. influenzae type b OMPC vaccine.
Methods
Study Participants
Navajo or Hopi infants living on the Navajo Indian Reservation were enrolled in the study on receiving their first immunization and after informed consent was obtained from their parents or guardians. Infants were excluded from the study if they had known or suspected immunodeficiency disease, a history of vaccination with any other H. influenzae vaccine, or a history contraindicating routine immunization with diphtheria–pertussis–tetanus (DPT) vaccine or the oral attenuated-poliovirus vaccine. The study protocol was approved by the Committee on Human Volunteers at the Johns Hopkins University School of Hygiene and Public Health, the Indian Health Service, the Navajo Health Boards, and the Hopi Tribal Health Department. The study began on July 1, 1988, and ended on August 2, 1990. Approximately 90 percent of the 9038 infants born at our study sites were available for recruitment. The remaining infants lived outside the reservation or in remote locations where accurate follow-up of clinical illnesses was not possible.
Randomization and Blinding
At each site infants were randomly assigned in blocks of 20 to receive either vaccine or placebo just before their first routine childhood immunization. The randomization code was not known to the investigators or to the children's parents or guardians until the study ended. The appearances of the vaccine and placebo were identical. Three lots of H. influenzae type b OMPC vaccine (1072, 1080, and 1085) were provided in lyophilized form and stored at 2 to 8°C. After reconstitution with 0.7 ml of diluent, each 0.5 ml of vaccine contained 15 μg of H. influenzae polysaccharide, 131 to 272 μg of a group B meningococcal OMPC, and 1 to 2 mg of lactose. The placebo vials contained 2 mg of lactose. The aluminum hydroxide diluent (1.5 ml per vial) contained 0.4 mg of aluminum and 49.8 μg of thimerosal per milliliter. The diluent was stored at 2 to 8°C.
Study Protocol
Infants were given the first injection of H. influenzae type b OMPC vaccine or placebo between the ages of 42 and 90 days. The protocol required the second injection of vaccine or placebo to be given between 70 and 146 days of age, at least 28 days after the first injection. However, the second injection was not withheld from infants who were first seen after the age of 146 days. Infants who were given the second dose after the age of 146 days were excluded from the strict efficacy analysis. The DPT and oral poliovirus vaccines were administered simultaneously with the H. influenzae type b OMPC vaccine or placebo, but in different thighs. When the study began, the Indian Health Service gave one of the licensed H. influenzae conjugate vaccines (composed of polyribosylribitol phosphate and diphtheria toxoid [PRP-D], ProHIBit, Connaught Laboratories) to all infants at the age of 18 months. After April 1990, when the recommendations for administering the licensed H. influenzae conjugate vaccines were revised by the American Academy of Pediatrics and the Immunization Practices Advisory Committee, either PRP-D or H. influenzae type b oligosaccharide nontoxic cross-reaction material of diphtheria toxin (HbOC, or HibTITER, Praxis Biologics) was given at the age of 15 months.
Laboratory Studies
Blood (3 ml) was obtained for the measurement of serum antibody to the H. influenzae capsular polysaccharide before the first and second immunizations, at 6 and 12 months of age, and before the dose of H. influenzae vaccine given at 15 to 18 months of age. Serum antibody to the H. influenzae capsular polysaccharide was assayed at Merck Sharp and Dohme Research Laboratories with a standardized radioimmunoassay.11 The physicians at the Indian Health Service were asked to obtain blood samples for culture from all infants with a temperature of ≤39.4°C (≥103°F). Samples of blood, cerebrospinal fluid, and urine were obtained for culture and detection of H. influenzae antigen in infants thought to have sepsis or meningitis.
Microbiologie Studies
Blood cultures were obtained by members of the hospital staff and processed in the various clinical laboratories according to standard methods.12 Normally sterile body fluids were cultured directly onto chocolate agar and incubated in a 5 percent carbon dioxide atmosphere.
Isolates of H. influenzae were sent from the respective clinical laboratories to the project laboratory in Whiteriver, Arizona, where their identities were confirmed on the basis of their reaction to H. influenzae antiserum, pattern of growth in the presence of factors X and V, and response to a biochemical panel (Microscan, Baxter Laboratories). The isolates were frozen at - 70°C in a glycerol-tryptic soy broth medium for separate confirmation with the same assays at Johns Hopkins, in Baltimore. Urine and serum samples from infants with suspected cases were also tested for H. influenzae capsular polysaccharide antigen with a latex agglutination assay (Directogen, Becton Dickinson). No patient had a positive antigen assay with negative cultures.
Definitions
Patients were considered to have been recruited if their parents or guardians gave written informed consent and to have been enrolled (intention-to-treat analysis) if they had received the first dose of vaccine or placebo. Each participant was considered to have reached an end point for study if he or she reached the age of 18 months, received a booster dose of H. influenzae vaccine, moved to a location where reliable follow-up was not possible, was given a diagnosis of H. influenzae disease, or died; the other end point was termination of the study. A definite case of invasive H. influenzae disease was considered to have occurred if H. influenzae was isolated from cerebrospinal fluid, blood, or other normally sterile body fluids. Aseptic meningitis was considered to be present if there were ≤8 leukocytes per cubic millimeter in a cerebrospinal fluid sample and negative bacterial cultures.
Monitoring of Adverse Reactions
All infants were observed for at least 15 minutes after each injection. The parents or guardians were asked to record the child's temperature daily and any reactions that occurred during the week after injection. They were asked to report any serious reaction or illness that occurred within one month after each injection. After each injection, members of the study staff visited 10 percent of the study participants at home on days 1 and 2 and 40 percent on day 7. Each child's medical chart was reviewed retrospectively for hospitalizations or serious medical conditions occurring within 30 days of vaccination.
Independent Monitoring of Study for Safety and Early Termination
An independent monitoring committee was appointed to advise the investigators when to stop the study either for reasons of safety or because the efficacy of the vaccine had been established. The chairperson of the monitoring committee was informed of any cases of anaphylaxis, urticaria, or seizures that occurred within eight days of an injection and of all deaths recorded during the study period. All definite cases of invasive H. influenzae disease were reported within 24 hours.
The committee met on August 2, 1990, after 23 definite cases of H. influenzae infection had occurred. It advised us to stop the trial because of the difference in the distribution of cases of H. influenzae disease between the vaccine and placebo groups. On two previous occasions the committee broke the study codes assigned to participants who died, to determine group assignment. The code was also broken for safety monitoring after the eighth case of invasive H. influenzae disease was reported.
Data Management and Statistical Analysis
A customized double-data-entry system was designed for this study with FOXPLUS software. P values were computed for contingency tables with Fisher's exact test or chi-square tests. The means were compared with t-tests. All confidence intervals were 95 percent confidence intervals. The confidence limits for the protective efficacy were calculated on the basis of the assumption that the number of cases in each group followed a Poisson distribution with parameters lambdav and lambdap in the vaccine and placebo groups, respectively. Conditional on the total number of cases (T), the number of cases in the vaccine group (V) is distributed binomially, with parameters T and u = (lambdav + lambdap).13 Exact 95 percent confidence limits were computed for u, and these values were transformed into confidence intervals for efficacy. SAS version 6 and EPIINFO version 5 were used for all statistical computations. A P value of 0.05 or less was considered to indicate statistical significance.
If the serum antibody level to H. influenzae type b capsular polysaccharide was below a detectable level (0.125 μg per milliliter), a value of 0.0625 μg per milliliter was assigned for the calculation of the geometric mean titers.
Results
Clinical Characteristics
From July 1, 1988, to August 2, 1990, 5190 infants were enrolled (intention to treat) and received vaccine (n = 2588) or placebo (n = 2602). Twenty-four recruited infants were excluded from the study before vaccination because they fulfilled one of the exclusion criteria. A total of 4161 (80 percent) of the enrolled infants received the second dose of vaccine (n = 2056) or placebo (n = 2105). Two hundred forty-nine children in the vaccine group and 250 in the placebo group had received their first dose and were still eligible to receive the second dose when the trial was terminated. In 26 of the 27 infants whose first vaccination was not given according to schedule, the vaccine was given no more than five days from the scheduled time (average, two). The remaining child received his first vaccination 15 days late. Fifteen children were excluded from the strict protocol analysis: 3 because they received an incorrect second dose and 12 because the dose given was too low (7 in the vaccine group and 5 in the placebo group).
There were no significant differences between the two groups in the mean age, ratio of male to female infants, ethnic background, number of doses of vaccine or placebo received, time between the first and second doses, or length of follow-up (Table 1Table 1
Selected Characteristics of the Infants Who Received at Least One Dose of H. influenzae Type b OMPC Vaccine or Placebo.*). Two children in the placebo group did not receive a second dose because preexisting medical conditions were diagnosed after the first dose. Four children did not receive a second dose because of a possible reaction to the first dose: one had an abnormal cry after receiving vaccine, and after receiving placebo two had seizures and one had hives.During the study, the mortality rates for both study participants and nonparticipants were the same (data not shown). Among the participants, there were eight deaths in each group. The monitoring committee concluded that none of these deaths were related to vaccine or placebo. The following causes of death were recorded on death certificates: in the vaccine group, three cases of sudden infant death syndrome and one case each of respiratory tract infection, viral illness, hepatic failure, Reye's syndrome, and midgut volvulus; and in the placebo group, two cases each of respiratory infection and viral illness and one case each of sudden infant death syndrome, accidental death, H. influenzae meningitis, and gastroenteritis. Sixteen children had seizures, nine in the vaccine group and seven in the placebo group. Seizures and deaths were not clustered according to the time after immunization.
Adverse Reactions
During the 30 days after vaccination there were 104 hospitalizations in the vaccine group and 106 in the placebo group. More than 50 analyses were performed to search for possible adverse reactions due to the vaccine. However, the only conditions that were significantly different and occurred at a rate of 1 percent or more in either group were observed after the second injection, as follows: viral infections, as diagnosed by physicians (8 in the vaccine group [0.5 percent] and 28 in the placebo group [1.6 percent]; P = 0.001 ), and conjunctivitis (34 in the vaccine group [2.0 percent] and 54 in the placebo group [3.1 percent]; P = 0.040). For each category of clinical symptoms we summarized the daily data gathered during home visits, to derive a weekly measure of symptoms; the infants were classified as having either no symptoms or one or more. On the basis of these data, there was a significant difference between the groups in the incidence of the following symptoms: areas of redness measuring less than 2.54 cm (1 in.) in diameter (48 in the vaccine group [3.3 percent] and 18 in the placebo group [1.2 percent]; P<0.001) and areas of swelling measuring less than 2.54 cm (1 in.) in diameter (91 in the vaccine group [6.2 percent] and 10 in the placebo group [0.7 percent]; P<0.001). Similar results were noted when parental reports were analyzed.
When the results of both vaccinations were combined, there was no significant difference in the mean maximal temperature in the 48 hours after the injection between the vaccine group and the placebo group (37.4°C [99.37°F] vs. 37.4°C [99.39°F]; P = 0.54) or in the percentage of children with a temperature above 38.9°C (102°F) (1.63 percent vs. 1.54 percent; P = 0.76). Analyses performed separately for first and second doses yielded similar results.
Antibody Response
Since a serum level of 0.15 μg of antibody to the H. influenzae type b capsular polysaccharide per milliliter has been proposed to be protective,14 we analyzed the data to determine the proportion of infants who had antibody levels above this value. Before the first dose of the vaccine 55 percent of infants had serum antibody levels to the H. influenzae type b capsular polysaccharide of less than 0.15 μg per milliliter (Table 2Table 2
Antibody Responses in Infants Vaccinated with H. influenzae Type b OMPC Vaccine or Placebo.*). Two months after the first and second doses of the vaccine 10 percent and 9 percent of the infants, respectively, had serum antibody levels below 0.15 μg per milliliter. Eight months after the second dose of the vaccine, however, 24 percent of the infants had serum antibody levels below 0.15 μg per milliliter.Incidence of Invasive H. influenzae Disease
We analyzed the incidence rates of H. influenzae disease during the first 15 months and the first 18 months of life, to reflect the changes in the H. influenzae vaccination policy of the Indian Health Service described above. When all subjects were included in an intention-to-treat analysis of cases occurring before the age of 18 months, 1 case was found in the vaccine group and 22 in the placebo group (P<0.001; point estimate of efficacy, 95 percent; 95 percent confidence interval, 72 to 99 percent) (Table 3Table 3
Efficacy Analysis of H. influenzae Type b OMPC Vaccine.). When only children receiving two doses were included, there were 14 cases in the placebo group (n = 2105) and 1 case in the vaccine group (n = 2056) (P<0.001; point estimate of efficacy, 93 percent; 95 percent confidence interval, 53 to 98 percent). When the intention-to-treat analysis was modified to include only the cases occurring before the age of 15 months, there were no cases in the vaccine group and 21 in the placebo group (P<0.001; point estimate of efficacy, 100 percent; 95 percent confidence interval, 81 to 100 percent). When this analysis was further restricted to include only children who had received two doses, there were no cases in the vaccine group and 13 in the placebo group (P<0.001; point estimate of efficacy, 100 percent; 95 percent confidence interval, 67 to 100 percent). Between the first and second doses, no cases of H. influenzae occurred in the vaccine group, whereas eight occurred in the placebo group (P = 0.005; point estimate of efficacy, 100 percent; 95 percent confidence interval, 41 to 100 percent). Two of these cases occurred in children who had passed the protocol date for their second dose.The one case of H. influenzae disease (osteomyelitis) that occurred in a vaccine recipient developed at 15 1/2 months of age, 368 days after the second immunization (Table 4Table 4
Cases of H. influenzae Type b, According to the Type of Disease, Age, and Vaccination Status.). The antibody levels against H. influenzae type b capsular polysaccharide in this infant were less than 0.125 μg per milliliter before the first vaccination, 2.86 μg per milliliter just before the second vaccination, 1.49 μg per milliliter two months later, 0.14 μg per milliliter at one year of age, and 1.35 μg per milliliter 42 days after the infection. Of the 22 cases of invasive H. influenzae disease that occurred in the placebo group, 13 (59 percent) were meningitis. The remaining infants had nonmeningitic infections. There were 15 cases of aseptic meningitis in the vaccine group and 13 cases in the placebo group (P = 0.70). There were 19 cases of invasive pneumococcal disease in the vaccine group and 13 in the placebo group (P = 0.29).Discussion
The results of this randomized, double-blind trial show that the H. influenzae type b OMPC vaccine was efficacious in preventing H. influenzae disease when two doses were administered two months apart beginning at the age of 6 to 12 weeks. A single dose of the vaccine was also protective for at least two months. Therefore, in populations in which a large proportion has H. influenzae disease before the age of six months, such as certain Native American populations, this vaccine should have a substantial effect on disease prevention. Even in the general U.S. population, 15 to 20 percent of the cases of H. influenzae disease (3000 to 4000 cases per year) occur before the age of six months.1 , 2 This vaccine can potentially prevent most of these cases and has minimal side effects.
In this double-blind, placebo-controlled trial, the H. influenzae type b OMPC vaccine had over 90 percent efficacy in preventing H. influenzae disease in infants. A previous study with a similar design demonstrated limited efficacy when another H. influenzae conjugate vaccine, PRP-D, was used in a Native American population in Alaska.15 In that study approximately 2000 infants were randomly assigned to receive vaccine or placebo at two, four, and six months of age. The overall incidence of H. influenzae disease was not reduced significantly in the vaccinated group as compared with the placebo group (6.0 vs. 9.6 cases per 1000 patient-years). There was no significant protective efficacy with the vaccine after one, two, or three doses; after three doses the point estimate of efficacy was only 35 percent.
In contrast, a large-scale open, prospective, randomized trial in Finland found that PRP-D was efficacious (point estimate of efficacy, 94 percent) in preventing H. influenzae disease.16 A total of 114,000 infants were randomly assigned to receive either one dose of PRP-D at the ages 3, 4, 6, and 14 to 18 months or a single dose at the age of 24 months. After three doses of vaccine, there were 4 cases of H. influenzae disease between the ages of 7 and 24 months in the group that received a total of four doses and 64 in the group that received a single dose at 24 months of age (point estimate of efficacy, 94 percent).
Recently, another H. influenzae conjugate vaccine, HbOC, was evaluated in a randomized open trial in a health maintenance organization in the United States.17 In that trial, infants assigned to the vaccine group received the vaccine at two, four, and six months of age, whereas the control group was not given the vaccine during the first year of life. In the prospective cohort analysis of the efficacy of three doses of vaccine, 12 cases of H. influenzae disease occurred in the unvaccinated children during 11,335 person-years of follow-up, as compared with no cases in the vaccinated children during 12,949 person-years of follow-up (point estimate of efficacy, 100 percent). However, three cases occurred during 6553 person-years of follow-up among infants who received a single dose of the vaccine. The results of these trials indicate that the efficacy of H. influenzae vaccines may vary from population to population.
In previous studies, we have demonstrated that as compared with children in the general U.S. population, children in two Native American populations have a diminished response to the unconjugated polysaccharide vaccine18 and to one of the H. influenzae conjugate vaccines.14 Since the H. influenzae type b OMPC vaccine was efficacious in preventing H. influenzae disease in the Navajo Indians, it should prevent disease in the general U.S. population, which is known to have better immune responses to H. influenzae vaccines.
The H. influenzae type b OMPC vaccine produces antibody levels to the H. influenzae type b capsular polysaccharide above 1 μg per milliliter in 60 to 70 percent of infants after a single dose, as demonstrated in this study and in previous studies.8 9 10 However, as seen in this study, there is only a marginal increase in antibody levels to the H. influenzae type b capsular polysaccharide after the second dose, as compared with those seen after a single dose. Nevertheless, this vaccine was efficacious in preventing H. influenzae disease before the age of 18 months. In this study, within eight months after the second dose of the H. influenzae type b OMPC vaccine, there was a threefold drop in the geometric mean antibody levels to the H. influenzae type b capsular polysaccharide. We did not measure the antibody responses to booster immunization at 12 to 15 months of age. Previous studies 8 , 19 have demonstrated that a booster dose at 12 and 18 months of age induced an 8-fold and a 15-fold increase in antibody levels, respectively. In a previous study, we immunized a cohort of Apache and Navajo infants at 2, 4, and 12 months of age.8 The geometric mean antibody levels to the H. influenzae type b capsular polysaccharide were 0.53 μg per milliliter before the 12-month dose and 8.38 μg per milliliter 1 month later. For children who are vaccinated at the ages of 2 and 4 months, these data suggest that it would be prudent to reimmunize them at the age of 12 months or soon thereafter. The one case of H. influenzae disease that occurred in a vaccine recipient might have been prevented if the infant had been reimmunized between 12 and 15 months of age.
We conclude that the H. influenzae type b OMPC vaccine prevents H. influenzae disease for at least 2 months after a single dose in infants 6 to 12 weeks of age and up to the age of 18 months when two doses of the vaccine are given 2 months apart. Widespread use of H. influenzae type b OMPC vaccine should virtually eliminate H. influenzae disease in the United States.
Supported by a grant from Merck Sharp and Dohme Research Laboratories. The opinions in this article do not necessarily reflect the views of the Indian Health Service.
Linda Capriotti is the only stockholder of Merck Sharp and Dohme among the authors not employed by the firm.
We are indebted to Drs. Neal Halsey, Richard Moxon, Claire Broome, George Brenneman, Kenrad Nelson, David Klein, and William Blackwelder for serving on the monitoring committee; to Drs. John Ryan and Lawrence Gould for technical advice; to Jack Armstrong, Cindy Rusk, Joan Staub, and Sally Szymanski for performing all radioimmunoassays for serum antibody to H. influenzae type b capsular polysaccharide; to Drs. Robert Daum, John Robbins, Juhani Eskola, Dan Granoff, Robert Black, and Bradley Sack for reviewing the manuscript; to the Johns Hopkins University nurses and Navajo field workers for assisting in all aspects of the study; to Mr. Michel Lincoln and Drs. Douglas Peter and Michael Everett for advice and support in conducting the trial; to the staff at all U.S. Public Health Service hospitals and clinics, the Sage Memorial Hospital, and Monument Valley Hospital on the Navajo Indian Reservation; to Stephen Garrett for maintaining the study code; to the Committee on Human Volunteers at Johns Hopkins University, the Health Boards of the Navajo Area Service Units, and the Navajo Area Research and Publications Committee for their ethical review of the protocol; to Brenda Gill and Carol Britenback for assistance in the preparation of the manuscript; and to the Navajo infants who participated in this study and to their parents.
Source Information
From the Center for American Indian and Alaskan Native Health, Department of International Health, and the Division of Pediatric Infectious Disease, Department of Pediatrics, Johns Hopkins University School of Hygiene and Public Health and the School of Medicine, Baltimore, Md. (M.S., M.W., R.R., M.H., M.B., J.G., M.C., D.S., J.H., W.N., L.C., J.S., M.O., R.K.); the Navajo Area Indian Health Service, Window Rock, Ariz. (S.G., D.H.); and Merck Sharp and Dohme Research Laboratories, West Point, Pa. (L.L., R.W.E., P.P.V., G.C., H.M., V.A.). Address reprint requests to Dr. Santosham at the Center for American Indian and Alaskan Native Health, Department of International Health, Johns Hopkins University School of Hygiene and Public Health, 615 N. Wolfe St., Baltimore, MD 21205.
- References
References
1
Broome
CrossRef | Web of Science | Medline2
Schlech
CrossRef | Web of Science | Medline3
Todd
Web of Science | Medline4
Ward
CrossRef | Web of Science | Medline5
Losonsky
CrossRef | Medline6
Coulehan
Web of Science | Medline7
Marburg
CrossRef | Web of Science8
Santosham
CrossRef | Web of Science | Medline9
Weinberg
CrossRef | Web of Science | Medline10
Shapiro
CrossRef | Web of Science | Medline11
Vella
Web of Science | Medline12
Lennette EH, Balows A, Hausler WJ Jr, Shadomy HJ, eds. Manual of clinical microbiology. 4th ed. Washington, D.C.: American Society for Microbiology, 1985.
13
Przyborowski
Web of Science14
Letson
CrossRef | Web of Science | Medline15
Ward
Full Text | Web of Science | Medline16
Eskola
Full Text | Web of Science | Medline17
Black
CrossRef | Web of Science | Medline18
Siber
Full Text | Web of Science | Medline19
Sood SK, Daum RS. Persistence of anticapsular antibody concentrations (ACAC) and effect of a booster dose at 18 months of age in infants immunized at 2 and 4 months of age with H. influenzae type b (Hib) PRPMeningococcal outer membrane protein conjugate vaccine (PRP-OMP). In: Program and abstracts of the 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, October 21–24, 1990. Washington. D.C: American Society for Microbiology, 1990:97
- Citing Articles (84)
Citing Articles
1
Robert Menzies, Ross Andrews. (2011) Immunisation issues for Indigenous Australian children. Journal of Paediatrics and Child Healthno-no
CrossRef2
Ron Dagan, Gregory Poland. (2010) World Pneumonia Day: Fighting pneumonia with safe and affordable vaccines. Vaccine 28:48, 7577-7578
CrossRef3
J. Eskola. (2010) Foresight in medicine: current challenges with Haemophilus influenzae type b conjugate vaccines. Journal of Internal Medicine 267:3, 241-250
CrossRef4
Hyunju Lee, Seokyung Hahn, Hoan Jong Lee, Kyung-Hyo Kim. (2010) Immunogenicity of Haemophilus influenzae Type b Conjugate Vaccines in Korean Infants: A Meta-analysis. Journal of Korean Medical Science 25:1, 90
CrossRef5
Robert I. Menzies, Rosalyn J. Singleton. (2009) Vaccine Preventable Diseases and Vaccination Policy for Indigenous Populations. Pediatric Clinics of North America 56:6, 1263-1283
CrossRef6
S. Ladhani, P. T. Heath, M. P. E. Slack, P. B. McIntyre, J. Diez-Domingo, J. Campos, R. Dagan, M. E. Ramsay, . (2009) Haemophilus influenzae serotype b conjugate vaccine failure in twelve countries with established national childhood immunization programmes. Clinical Microbiology and Infection
CrossRef7
George H Swingler, Desiree Michaels, Gregory GD Hussey, George H Swingler. 2009. Conjugate vaccines for preventing Haemophilus influenzae type B infections. .
CrossRef8
Renuka Verma, Margaret C. Fisher. (2009) Bacterial meningitis vaccines: Not just for kids. Current Infectious Disease Reports 11:4, 302-308
CrossRef9
Caroline L. Trotter, Jodie McVernon, Mary E. Ramsay, Cynthia G. Whitney, E. Kim Mulholland, David Goldblatt, Joachim Hombach, Marie-Paule Kieny. (2008) Optimising the use of conjugate vaccines to prevent disease caused by Haemophilus influenzae type b, Neisseria meningitidis and Streptococcus pneumoniae. Vaccine 26:35, 4434-4445
CrossRef10
Shaun K Morris, William J Moss, Neal Halsey. (2008) Haemophilus influenzae type b conjugate vaccine use and effectiveness. The Lancet Infectious Diseases 8:7, 435-443
CrossRef11
MarkAlain Dery, Rodrigo Hasbun. (2007) Changing epidemiology of bacterial meningitis. Current Infectious Disease Reports 9:4, 301-307
CrossRef12
Abdullah H. Baqui, Shams El Arifeen, Samir K. Saha, Lars??ke Persson, K Zaman, Bradford D. Gessner, Lawrence H. Moulton, Robert E. Black, Mathuram Santosham. (2007) Effectiveness of Haemophilus influenzae Type B Conjugate Vaccine on Prevention of Pneumonia and Meningitis in Bangladeshi Children. The Pediatric Infectious Disease Journal 26:7, 565-571
CrossRef13
Guilherme S. Ribeiro, Josilene B.T. Lima, Joice N. Reis, Edilane L. Gouveia, Soraia M. Cordeiro, Tatiana S. Lobo, Ricardo M. Pinheiro, Cássio T. Ribeiro, Alan B. Neves, Kátia Salgado, Hagamenon R. Silva, Mitermayer G. Reis, Albert I. Ko. (2007) Haemophilus influenzae meningitis 5 years after introduction of the Haemophilus influenzae type b conjugate vaccine in Brazil. Vaccine 25:22, 4420-4428
CrossRef14
George H Swingler, Desiree Michaels, Gregory GD Hussey, George H Swingler. 2007. Conjugate vaccines for preventing Haemophilus influenzae type B infections. .
CrossRef15
Hyunju Lee, So Eun Park, Soo Young Lim, Kyong Min Choi, Hoan Jong Lee, Kyung Hyo Kim. (2007) Antibody prsistence after Haemophilus influenzae type b (Hib) primary vaccination and response to boosters in Korean children. Korean Journal of Pediatrics 50:5, 449
CrossRef16
Kyung Hyo Kim, Soo Young Lim. (2007) Validation of enzyme immunoassay for the quantitative measurement of human IgG antibodies specific for Haemophilus influenzae Type b capsular polysaccharide. Korean Journal of Pediatrics 50:2, 143
CrossRef17
Jacqueline L. Deen, John D. Clemens. (2006) Issues in the design and implementation of vaccine trials in less developed countries. Nature Reviews Drug Discovery 5:11, 932-940
CrossRef18
Kyung Hyo Kim. (2006) Present status and prospects of Haemophilus influenzae type b(Hib) immunization. Korean Journal of Pediatrics 49:3, 242
CrossRef19
Aruna Chandran, James P Watt, Mathuram Santosham. (2005) Prevention of Haemophilus influenzae type b disease: past success and future challenges. Expert Review of Vaccines 4:6, 819-827
CrossRef20
Angela J. Peck, Robert C. Holman, Aaron T. Curns, Jairam R. Lingappa, James E. Cheek, Rosalyn J. Singleton, Karen Carver, Larry J. Anderson. (2005) Lower Respiratory Tract Infections Among American Indian and Alaska Native Children and the General Population of U.S. Children. The Pediatric Infectious Disease Journal 24:4, 342-351
CrossRef21
E. V. Millar, K. L. O'Brien, J. P. Watt, J. Lingappa, R. Pallipamu, N. Rosenstein, D. Hu, R. Reid, M. Santosham. (2005) Epidemiology of Invasive Haemophilus influenzae Type A Disease among Navajo and White Mountain Apache Children, 1988-2003. Clinical Infectious Diseases 40:6, 823-830
CrossRef22
Joseph H. Antin, Eva C. Guinan, David Avigan, Robert J. Soiffer, Robin M. Joyce, Victoria J. Martin, Deborah C. Molrine. (2005) Protective antibody responses to pneumococcal conjugate vaccine after autologous hematopoietic stem cell transplantation. Biology of Blood and Marrow Transplantation 11:3, 213-222
CrossRef23
Eric Mallet, Bernd H Belohradsky, Rosanna Lagos, Leif Gothefors, Patrice Camier, Jean-Pierre Carrière, Güler Kanra, Agnès Hoffenbach, Jacques Langue, François Undreiner, François Roussel, Philippe Reinert, Carl-Erik Flodmark, Silvia Stojanov, Johannes Liese, Myron M Levine, Alma Muñoz, Florian Schödel, Luc Hessel. (2004) A liquid hexavalent combined vaccine against diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type B and hepatitis B: review of immunogenicity and safety. Vaccine 22:11-12, 1343-1357
CrossRef24
EUGENE D. SHAPIRO. (2004) Case-control studies of the effectiveness of vaccines: validity and assessment of potential bias. The Pediatric Infectious Disease Journal 23:2, 127-131
CrossRef25
T. Kilpi, H. Ahman, J. Jokinen, K. S. Lankinen, A. Palmu, H. Savolainen, M. Gronholm, M. Leinonen, T. Hovi, J. Eskola, H. Kayhty, N. Bohidar, J. C. Sadoff, P. H. Makela, . (2003) Protective Efficacy of a Second Pneumococcal Conjugate Vaccine against Pneumococcal Acute Otitis Media in Infants and Children: Randomized, Controlled Trial of a 7-Valent Pneumococcal Polysaccharide-Meningococcal Outer Membrane Protein Complex Conjugate Vaccine in 1666 Children. Clinical Infectious Diseases 37:9, 1155-1164
CrossRef26
Luis Jódar, Jay Butler, George Carlone, Ron Dagan, David Goldblatt, Helena Käyhty, Keith Klugman, Brian Plikaytis, George Siber, Robert Kohberger, Ih Chang, Thomas Cherian. (2003) Serological criteria for evaluation and licensure of new pneumococcal conjugate vaccine formulations for use in infants. Vaccine 21:23, 3265-3272
CrossRef27
P Helena Mäkelä, Helena Käyhty. (2002) Evolution of conjugate vaccines. Expert Review of Vaccines 1:3, 399-410
CrossRef28
Jairam R. Lingappa, Nancy Rosenstein, Elizabeth R. Zell, Kathleen A. Shutt, Anne Schuchat, Bradley A. Perkins. (2001) Surveillance for meningococcal disease and strategies for use of conjugate meningococcal vaccines in the United States. Vaccine 19:31, 4566-4575
CrossRef29
R. C. Holman, A. T. Curns, S. F. Kaufman, J. E. Cheek, R. W. Pinner, L. B. Schonberger. (2001) Trends in infectious disease hospitalizations among American Indians and Alaska Natives. American Journal of Public Health 91:3, 425-431
CrossRef30
ERIC MALLET, PASCAL FABRE, EMMANUELLE PINES, HERV?? SALOMON, TED STAUB, FLORIAN SCH??DEL, PAUL MENDELMAN, LUC HESSEL, GEORGE CHRYSSOMALIS, EMMANUEL VIDOR, AGN??S HOFFENBACH. (2000) Immunogenicity and safety of a new liquid hexavalent combined vaccine compared with separate administration of reference licensed vaccines in infants. The Pediatric Infectious Disease Journal 19:12, 1119-1127
CrossRef31
E. V. Millar, K. L. O'Brien, O. S. Levine, S. Kvamme, R. Reid, M. Santosham. (2000) Toward elimination of Haemophilus influenzae type B carriage and disease among high-risk American Indian children. American Journal of Public Health 90:10, 1550-1554
CrossRef32
A.Dale Horne, Peter A. Lachenbruch, Karen L. Goldenthal. (2000) Intent-to-treat analysis and preventive vaccine efficacy. Vaccine 19:2-3, 319-326
CrossRef33
K. Mulholland. (2000) Evaluation of Vaccines to Prevent Childhood Pneumonia: Lessons Relevant to Planning Tuberculosis Vaccine Trials. Clinical Infectious Diseases 30:Supplement 3, S206-S209
CrossRef34
S. Guthridge, P. McIntyre, D. Isaacs, M. Hanlon, M. Patel. (2000) 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. Vaccine 18:23, 2584-2591
CrossRef35
Maurice R Hilleman. (2000) Vaccines in historic evolution and perspective: a narrative of vaccine discoveries. Vaccine 18:15, 1436-1447
CrossRef36
D. Goldblatt. (2000) Conjugate vaccines. Clinical and Experimental Immunology 119:1, 1-3
CrossRef37
ORIN S. LEVINE, ROSANNA LAGOS, ALMA MUÑOZ, JULIA VILLAROEL, ANA MARÍA ALVAREZ, PAULINA ABREGO, MYRON M. LEVINE. (1999) Defining the burden of pneumonia in children preventable by vaccination against Haemophilus influenzae type b. The Pediatric Infectious Disease Journal 18:12, 1060-1064
CrossRef38
Juhani Eskola, Joel Ward, Ron Dagan, David Goldblatt, Fred Zepp, Claire-Anne Siegrist. (1999) Combined vaccination of Haemophilus influenzae type b conjugate and diphtheria-tetanus-pertussis containing acellular pertussis. The Lancet 354:9195, 2063-2068
CrossRef39
Jay D Wenger, Jose-Luis DiFabio, Jose Mauricio Landaverde, Orin S Levine, Taki Gaafar. (1999) Introduction of Hib conjugate vaccines in the non-industrialized world: experience in four ‘newly adopting’ countries. Vaccine 18:7-8, 736-742
CrossRef40
Alexander H. Lucas, Donald C. Reason. (1999) Polysaccharide vaccines as probes of antibody repertoires in man. Immunological Reviews 171:1, 89-104
CrossRef41
Heikki Peltola. (1999) PROPHYLAXIS OF BACTERIAL MENINGITIS. Infectious Disease Clinics of North America 13:3, 685-710
CrossRef42
Maurice R. Hilleman. (1999) Personal historical chronicle of six decades of basic and applied research in virology, immunology, and vaccinology. Immunological Reviews 170:1, 7-27
CrossRef43
Annie W Sturgess, Kay Rush, Ronald J Charbonneau, James I Lee, David J West, Robert D Sitrin, John P Hennessey. (1999) Haemophilus influenzae type b conjugate vaccine stability: catalytic depolymerization of PRP in the presence of aluminum hydroxide. Vaccine 17:9-10, 1169-1178
CrossRef44
H S Jafari, W G Adams, K A Robinson, B D Plikaytis, J D Wenger. (1999) Efficacy of Haemophilus influenzae type b conjugate vaccines and persistence of disease in disadvantaged populations. The Haemophilus Influenzae Study Group.. American Journal of Public Health 89:3, 364-368
CrossRef45
Michael P Flanagan, J.Gabriel Michael. (1999) Oral immunization with a Streptococcal pneumoniae polysaccharide conjugate vaccine in enterocoated microparticles induces serum antibodies against type specific polysaccharides. Vaccine 17:1, 72-81
CrossRef46
Ron Dagan, Drora Fraser, Malvina Roitman, Paul Slater, Emilia Anis, Shai Ashkenazi, Imad Kassis, Dan Miron, Alexander Leventhal. (1999) Effectiveness of a nationwide infant immunization program against Haemophilus influenzae b. Vaccine 17:2, 134-141
CrossRef47
G. SCOTT GIEBINK. (1999) Otitis Media: The Chinchilla Model1. Microbial Drug Resistance 5:1, 57-72
CrossRef48
ORIN S. LEVINE, BENJAMIN SCHWARTZ, NATHANIEL PIERCE, MARK KANE. (1998) Development, evaluation and implementation of Haemophilus influenzae type b vaccines for young children in developing countries: current status and priority actions. The Pediatric Infectious Disease Journal 17:Supplement, S95-S113
CrossRef49
PAUL T. HEATH. (1998) Haemophilus influenzae type b conjugate vaccines: a review of efficacy data. The Pediatric Infectious Disease Journal 17:Supplement, S117-S122
CrossRef50
HEIKKI PELTOLA. (1998) Haemophilus influenzae type b disease and vaccination in Europe: lessons learned. The Pediatric Infectious Disease Journal 17:Supplement, S126-S132
CrossRef51
Maurice R. Hilleman. (1998) Six decades of vaccine development—a personal history. Nature Medicine 4:5s, 507-514
CrossRef52
M. Almuneef, Z. Memish, Y. Khan, A. Kagallwala, M. Alshaalan. (1998) Childhood bacterial meningitis in Saudi Arabia. Journal of Infection 36:2, 157-160
CrossRef53
M. Hadida, L. E. Cuevas, A. Moghadami, M. Baccoosh, R. Q. Gurgel, C. A. Hart. (1998) Immunogenicity of Haemophilus influenzae-diphtheria CRM197 protein conjugate vaccine (HbOC) in Libyan infants. Tropical Medicine and International Health 3:2, 95-99
CrossRef54
MICHAEL E. PICHICHERO, THOMAS LATIOLAIS, DAVID I. BERNSTEIN, PHILIP HOSBACH, EDWARD CHRISTIAN, EMMANUEL VIDOR, CARLTON MESCHIEVITZ, ROBERT S. DAUM. (1997) Vaccine antigen interactions after a combination diphtheria-tetanus toxoid-acellular pertussis/purified capsular polysaccharide of Haemophilus influenzae type b-tetanus toxoid vaccine in two-, four- and six-month-old infants. The Pediatric Infectious Disease Journal 16:9, 863-870
CrossRef55
SIGURVEIG T. SIGURDARDOTTIR, GESTUR VIDARSSON, THOROLFUR GUDNASON, SVEINN KJARTANSSON, KARL G. KRISTINSSON, STEINN JONSSON, HELGI VALDIMARSSON, GERALD SCHIFFMAN, RACHEL SCHNEERSON, INGILEIF JONSDOTTIR. (1997) Immune responses of infants vaccinated with serotype 6B pneumococcal polysaccharide conjugated with tetanus toxoid. The Pediatric Infectious Disease Journal 16:7, 667-674
CrossRef56
DAVID J. WEST, TERESA M. HESLEY, LESLIE C. JONAS, LOUISA K. FEELEY, STEVEN R. BIRD, PAMELA BURKE, JERALD C. SADOFF. (1997) Safety and immunogenicity of a bivalent Haemophilus influenzae type b/hepatitis B vaccine in healthy infants. The Pediatric Infectious Disease Journal 16:6, 593-599
CrossRef57
Paul M. Mendelman, Louisa Feeley, Steven Bird, Ted Staub, Holly Matthews, Mark A. Del Beccaro, Gary Overturf, Ann Lee, Ronald Ellis, Joan Staub, Sally Szymanski, John Donnelly, John P. Hennessey, Peter Kniskern. (1997) Immunogenicity and safety of Haemophilus influenzae type b polysaccharide-Neisseria meningitidis conjugate vaccine in 7.5 μg liquid formulation: a comparison of three lots with the 15.0 μg lyophilized formulation. Vaccine 15:6-7, 775-781
CrossRef58
Robert Booy, Paul T Heath, Mary PE Slack, Norman Begg, E Richard Moxon. (1997) Vaccine failures after primary immunisation with Haemophilus influenzae type-b conjugate vaccine without booster. The Lancet 349:9060, 1197-1202
CrossRef59
SN AMERATUNGA, DR LENNON, B ENTWISTLE, E ROBINSON, RV AMERATUNGA. (1997) The immunogenicity of Haemophilus influenzae: Meningococcal protein conjugate vaccine in Polynesian and non-Polynesian New Zealand infants. Journal of Paediatrics and Child Health 33:2, 138-141
CrossRef60
Kim Mulholland, Stephen Hilton, Richard Adegbola, Stanley Usen, Anslem Oparaugo, Charles Omosigho, Martin Weber, Ayo Palmer, Gisela Schneider, Kebba Jobe, George Lahai, Shabbar Jaffar, Ousman Secka, Kimi Lin, Chantal Ethevenaux, Brian Greenwood. (1997) Randomised trial of Haemophilus influenzae type-b tetanus protein conjugate for prevention of pneumonia and meningitis in Gambian infants. The Lancet 349:9060, 1191-1197
CrossRef61
Ramesh K. Sood, Ali Fattom, Viliam Pavliak, Robert B. Naso. (1996) Capsular polysaccharide-protein conjugate vaccines. Drug Discovery Today 1:9, 381-387
CrossRef62
KIM KRISTENSEN, ANETTE GYHRS, BIRGITTE LAUSEN, TORBEN BARINGTON, CARSTEN HEILMANN. (1996) Antibody response to Haemophilus influenzae type b capsular polysaccharide conjugated to tetanus toxoid in preterm infants. The Pediatric Infectious Disease Journal 15:6, 525-529
CrossRef63
HEIDI ÅHMAN, HELENA KÄYHTY, PIRJO TAMMINEN, ARJA VUORELA, FRANK MALINOSKI, JUHANI ESKOLA. (1996) Pentavalent pneumococcal oligosaccharide conjugate vaccine PncCRM is well-tolerated and able to induce an antibody response in infants. The Pediatric Infectious Disease Journal 15:2, 134-139
CrossRef64
J. Eskola. (1995) Use of conjugate vaccines to prevent meningitis caused by Haemophilus influenzae type b or Streptococcus pneumoniae. Journal of Hospital Infection 30, 313-321
CrossRef65
K. Kristensen, T. Barington, T. Pressler, C. Heilmann. (1995) Characterization of the antibody response to a Haemophilus influenzae type b conjugate vaccine in children with recurrent lower respiratory tract infection. Allergy 50:6, 528-531
CrossRef66
JOHN CLEMENS, RUTH BRENNER, MALLA RAO. (1995) Interactions between PRP-T Vaccine against Haemophilus influenzae Type b and Conventional Infant Vaccines.. Annals of the New York Academy of Sciences 754:1 Combined Vacc, 255-266
CrossRef67
DAN M. GRANOFF, ALEXANDER H. LUCAS. (1995) Laboratory Correlates of Protection against Haemophilus influenzae Type b Disease.. Annals of the New York Academy of Sciences 754:1 Combined Vacc, 278-288
CrossRef68
David W. Scheifele, William Meekison, Roland Guasparini, Ann Roberts, Luis Barreto, John Thipphawong, Sharon Wiltsey. (1995) Evaluation of booster doses of Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in 18-month-old children. Vaccine 13:1, 104-108
CrossRef69
Juhani Eskola, Helena Käyhty. (1995) New Vaccines for Prevention of Pneumococcal Infections. Annals of Medicine 27:1, 53-56
CrossRef70
Kathryn E. Stein. (1994) Glycoconjugate Vaccines: What Next?. International Journal of Technology Assessment in Health Care 10:01, 167
CrossRef71
Peter McIntyre, Jane Hall, Stephen Leeder. (1994) An economic analysis of alternatives for childhood immunisation against Haemophilus influenzae type b disease. Australian Journal of Public Health 18:4, 394-400
CrossRef72
P. Helena Mäkelä. (1994) Capsular Polysaccharide and Conjugate Vaccines. Zentralblatt für Bakteriologie 281:3, 334-339
CrossRef73
P. McINTYRE. (1994) Vaccines against invasive Haemophilus influenzae type b disease. Journal of Paediatrics and Child Health 30:1, 14-18
CrossRef74
Chao-Ming Tsai, Xin-Xing Gu, R.Andrew Byrd. (1994) Quantification of polysaccharide in Haemophilus influenzae type b conjugate and polysaccharide vaccines by high-performance anion-exchange chromatography with pulsed amperometric detection. Vaccine 12:8, 700-706
CrossRef75
Birger Trollfors. (1994) Cost-benefit Analysis of General Vaccination against Haemophilus influenzae type b in Sweden. Scandinavian Journal of Infectious Diseases 26:5, 611-614
CrossRef76
George W. Williams, Robert L. Davis, Albert J. Getson, A. Lawrence Gould, Irving K. Hwang, Holly Matthews, Weichung Joseph Shih, Steven M. Snapinn, Karen L. Walton-Bowen. (1993) Monitoring of clinical trials and interim analyses from a drug Sponsor's point of view. Statistics in Medicine 12:5-6, 481-492
CrossRef77
Alain Gervaix, Susanne Suter. (1993) Need for prevention of invasive Haemophilus influenzae type b infections in Geneva, Switzerland. Vaccine 11, S34-S37
CrossRef78
Mathuram Santosham. (1993) Prevention of Haemophilus influenzae type b disease. Vaccine 11, S52-S57
CrossRef79
G.B. Calandra, L.J. Lukacs, L.C. Jonas, M. Santosham, J.I. Ward, D.P. Greenberg, R.S. Daum, H. Matthews, P.P. Vella, J.L. Ryan. (1993) Anti-PRP antibody levels after a primary series of PRP-OMPC and persistence of antibody titres following primary and booster doses. Vaccine 11, S58-S62
CrossRef80
A. Barra, R. Dagan, J.L. Preud'homme, A. Bajart, B. Danve, B. Fritzell. (1993) Characterization of the serum antibody response induced by Haemophilus influenzae type b tetanus protein-conjugate vaccine in infants receiving a DTP-combined vaccine from 2 months of age. Vaccine 11:10, 1003-1006
CrossRef81
Desforges, Jane F., , Peter, Georges, . (1992) Childhood Immunizations. New England Journal of Medicine 327:25, 1794-1800
Full Text82
J. HANNA. (1992) The epidemiology and prevention of Haemophilus influenzae infections in Australian Aboriginal children. Journal of Paediatrics and Child Health 28:5, 354-361
CrossRef83
H. Peltola, T. Kilpi, M. Anttila, H. Peltola, T. Kilpi. (1992) Rapid disappearance of Haemophilus influenzae type b meningitis after routine childhood immunisation with conjugate vaccines. The Lancet 340:8819, 592-594
CrossRef84
Mitchell G. Scott, Hans G. Zachalv, Moon H. Nahm. (1992) The Human Antibody V Region Repertoire to the Type B Capsular Polysaccharide of Haemophilus influenzae. International Reviews of Immunology 9:1, 45-55
CrossRef
