Conjugate Vaccine In Infants Research Articles

Clinical and immunologic responses to Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in infants injected at 3, 5, 7, and 18 months of age

The safety and immunogenicity of Haemophilus influenzae type b-tetanus toxoid conjugate vaccine (Hib-TT) were evaluated in 77 healthy infants receiving injections at 3, 5, 7, and 18 months of age. No serious local or systemic reactions were noted. After the first injection the geometric mean Hib antibody level rose to 0.55 micrograms/ml, and each subsequent injection elicited a statistically significant rise in the geometric mean. The percentage of vaccinees with Hib antibody levels greater than 0.15 micrograms/ml serum was 75.5% after the first, 97.4% after the second, and 100% after the third Hib-TT injection. This percentage fell to 90.9% at 18 months of age but rose again to 100% after the fourth injection. Control infants (n = 10) injected with diphtheria-tetanus toxoid-pertussis vaccine only had nondetectable levels after the second injection. Hib-TT elicited increases of Hib antibody in all isotypes: IgG greater than IgM greater than IgA. Among IgG subclasses the highest increases were of IgG1. All vaccinated subjects had greater than 0.01 U/ml of TT antibody (estimated protective level) throughout the study. We conclude that Hib-TT, injected at 3, 5, 7, and 18 months, is safe and induces protective levels of antibodies during the age of highest incidence of meningitis caused by Hib.

The Epidemiology and Prevention of Disease Caused by Haemophilus influenzae Type b

Disease caused by H. influenzae type b is a world-wide problem of major proportions that affects both developed and developing countries. Young children are at particularly high risk of developing serious invasive infections. There has been tremendous recent progress in the development of vaccines that are immunogenic even in young infants. Clinical trials have demonstrated the efficacy of these polysaccharide-protein conjugate vaccines in infants. Two of these vaccines have been licensed in the United States for use in infants, and licensure of a third conjugate vaccine is expected soon. Many questions still remain to be answered. Are there significant differences in the efficacy for infants of the different licensed conjugate vaccines? Are the differences in the recommended schedules of immunization for the different vaccines justified? Would a combination of an initial dose of PRP-OMP (which is the most immunogenic vaccine in 2-month-old children) followed by subsequent doses of HbOC or PRP-T provide better overall protection than a schedule that uses only a single vaccine? Although much more research remains to be done, these vaccines, which have been recommended for routine universal immunization of infants in the United States, give us the capability of effectively preventing this potentially devastating infection of children.

Immunogenicity of Haemophilus influenzae Type b Polysaccharide-Neisseria meningitidis Outer Membrane Protein Conjugate Vaccine in 2- to 6-Month-Old Infants

Fifty infants, 2 to 6 months of age, were vaccinated with Haemophilus influenzae type b capsular polysaccharide covalently linked to an outer membrane protein from Neisseria meningitidis group B. Subjects were given two injections and were randomly assigned to receive the injections separated by 1 or 2 months. Each dose contained 15 micrograms of polysaccharide and 51 micrograms of protein, or approximately twice the amount of polysaccharide as used in our previous trial (Lancet 1986;2:299). Fevers of 38.0 degrees to 38.8 degrees C developed in three infants (6%) within 24 hours after vaccination, but there were no other notable reactions. Following one injection, the geometric mean antibody concentration increased from 0.13 micrograms/mL in preimmune serum to 1.50 micrograms/mL in serum obtained 1 to 2 months later (P less than .001). After a second injection, there was a further increase in serum antibody (geometric mean = 3.11 micrograms/mL, P less than .007). The geometric mean antibody concentration of the group reimmunized 2 months after the first injection was higher than that in the group reimmunized after 1 month (3.95 v 2.32 micrograms/mL, P = .05, by analysis of covariance with age as the covariant). These data confirm our previous preliminary observations on the safety and immunogenicity of this new conjugate vaccine in infants 2 to 6 months of age. The data suggest that a 2-month interval between the first and second injections results in higher levels of serum antibody than a 1-month interval.

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.

Persistence of antibody and response to booster dose of Haemophilus influenzae type b polysaccharide diphtheria toxoid conjugate vaccine in infants immunized at 9 to 15 months of age

At approximately 2 years of age, 27 infants previously immunized at 9 to 15 months of age with two doses of polyribosylribitol phosphate-diphtheria toxoid conjugate vaccine (PRP-D) and 23 infants immunized with polyribosylribitol phosphate (PRP) vaccine were given a single injection of PRP-D. Pre- and post-immunization sera were obtained. No serious local or systemic reactions were observed. The PRP-D recipients had a geometric mean anti-PRP antibody level of 4.8 micrograms/ml 1 month after the second primary injection, retained 1.2 microgram/ml 1 year later, and had a level of 71 micrograms/ml after the booster immunization. In contrast, PRP recipients had a geometric mean level of 0.083 microgram/ml 1 month after the second primary injection, retained 0.042 microgram/ml 1 year later, and after a single dose of PRP-D at approximately 2 years of age had a geometric mean level of 8.6 micrograms/ml. The significantly higher antibody response in the prior PRP-D recipients suggests the recall of immunologic memory induced by the PRP-D vaccine.

Safety and immunogenicity of haemophilus influenzae type b-polysaccharide diphtheria toxoid conjugate vaccine in infants 9 to 15 months of age

Sixty 9- to 15-month-old infants were randomly assigned to receive two doses, 1 month apart, of a Haemophilus influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) or PRP vaccine, each containing 20 micrograms PRP. There were no significant local or systemic reactions. After one dose of PRP-D, 93% of the subjects attained levels of greater than or equal to 0.15 microgram/ml and 59% achieved greater than or equal to 1 microgram/ml antibody protein. These percentages rose to 100% and 86%, respectively, after the second dose, at which time the geometric mean titer of anti-PRP antibody was 4.8 micrograms/ml. IgG anti-PRP levels were 4.3 times higher than IgM. The proportion of IgG to IgM antibody induced by PRP-D increased with age. After two doses, 33% of the PRP recipients responded with a level of greater than or equal to 0.15 microgram/ml and only 19% responded to a level of greater than or equal to 1.0 microgram/ml. One year later, all of the PRP-D recipients tested still had greater than or equal to 0.15 microgram/ml and more than half had greater than or equal to 1.0 microgram/ml antibody protein.