Increasing doses of purified influenza virus hemagglutinin and subvirion vaccines enhance antibody responses in the elderly.

The reactogenicities and immunogenicities of two influenza virus vaccines were compared in a placebo-controlled clinical trial among healthy ambulatory persons > or = 65 years old (mean age, 72 years). Volunteers were assigned randomly to receive 15-, 45-, or 135-micrograms doses of monovalent influenza A/Taiwan (H1N1) hemagglutinin (HA) or subvirion (SV) vaccine intramuscularly or a placebo. Increasing doses of SV vaccine were associated with a higher rate of injection site discomfort (P < 0.05; chi-square test for linear trend), but all doses of both vaccines were well tolerated. Increasing the dose of the HA or the SV vaccine resulted in increasingly higher postimmunization levels of serum hemagglutination inhibition and neutralizing antibody levels (P < 0.001; multiple linear regression). Mean serum antibody titers at 1 month increased two- to threefold with a ninefold increase in dose; the frequencies of fourfold or greater rises in titer likewise increased. An increase in the dose of the HA or the SV vaccine also resulted in increased frequencies of rises in immunoglobulin A or G antibody titers in nasal wash specimens. The frequencies increased approximately twofold for each vaccine with a ninefold increase in the dose. These data suggest that increasing the HA vaccine dose is a promising approach to the development of improved influenza virus vaccines for use in elderly people.

Immunogenicity and safety of Haemophilus influenzae type b-tetanus protein conjugate vaccine alone or mixed with diphtheria-tetanus-pertussis vaccine in infants.

Haemophilus capsular polysaccharide-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-pertussis (DTP) vaccines were administered in a single syringe (group 1) or separate syringes (group 2) to 284 infants at 2, 4, and 6 months of age. Group 1 infants had a slightly greater incidence of local reactions. Systemic reactions were similar. The geometric mean titers of polyribosylribitol phosphate (PRP) serum antibody concentrations after the third dose of PRP-T vaccine were 4.8 and 4.3 micrograms/ml for groups 1 and 2, respectively. Antibody responses to DTP antigens were also similar. The immunogenicity and safety of the PRP-T and DTP vaccines are equivalent when the vaccines are administered in separate syringes or the same syringe to infants.

Immunogenicity of Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in children with sickle hemoglobinopathy or malignancies, and after systemic Haemophilus influenzae type b infection.

To determine the immunogenicity of Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in specific populations at risk, we administered vaccine to children with sickle cell anemia (n = 19; mean age, 18.3 months, malignancies (n = 18; mean age, 43.1 months), or a recent history of systemic H. influenzae type b infection (n = 17; mean age, 11.9 months). After one dose of polyribosylribitol phosphate-tetanus toxoid conjugate vaccine the geometric mean titers for polyribosylribitol phosphate antibody were 4.8 micrograms/ml (14/19 greater than 1 microgram/ml), 1.4 micrograms/ml (9/18 greater than 1 microgram/ml), and 5.6 micrograms/ml (15/17 greater than 1 microgram/ml) in these three groups, respectively. Children with sickle cell anemia or a recent history of systemic H. influenzae type b infection had polyribosylribitol phosphate antibody levels comparable to those of normal children of similar age after one or two doses of polyribosylribitol phosphate-tetanus toxoid conjugate vaccine. We conclude that this vaccine is immunogenic in children with underlying conditions associated with an increased risk of H. influenzae type b infection.

Immunogenicity of the Haemophilus influenzae type b capsular polysaccharide conjugate vaccine in children after systemic Haemophilus influenzae type b infections.

We immunized 24 patients (mean age 15.2 +/- 9.3 months) with polyribosylribitol phosphate-diphtheria toxoid conjugate vaccine (PRP-D) 2 months after a systemic Haemophilus influenzae type b infection. Children less than 24 months of age were immunized twice. Serum was obtained for antibody to PRP before and 1 or 2 months after immunization. Three of five children greater than 24 months of age and three of six children 18 to 24 months of age developed greater than 1 microgram/ml of antibody after immunization, and geometric mean postimmunization levels were significantly greater than preimmunization levels for both groups. However, two children who failed to respond to conventional PRP vaccine did not respond as expected to one dose of PRP-D. For children 7 to 17 months of age, the geometric mean PRP antibody levels increased as follows: preimmunization, 0.05 micrograms/ml; after the first dose, 0.28 micrograms/ml (p = 0.003); and after the second dose, 3.39 micrograms/ml (p = 0.001). Of 13 children, 10 developed antibody values greater than 1.0 micrograms/ml. PRP conjugate vaccines are immunogenic in young children who have not developed protective PRP antibody levels after a systemic H. Influenzae type b infection.