Anti-polyribosylribitol Phosphate Antibodies Research Articles

Immunogenicity of three Haemophilus influenzae type b protein conjugate vaccines in HIV seropositive adults and analysis of predictors of vaccine response

HIV-seropositive adults may be at increased risk of infection due to Haemophilus influenzae type b (Hib) as compared with HIV-seronegative adults. Protein conjugate vaccines have been demonstrated to induce protective levels of antibodies against Hib in immunocompetent infants and also in HIV-seropositive infants. In this study we determined the immunogenicity of three protein conjugate Hib vaccines (PRP-D, HbOC, HbNOMP) in 135 HIV-seropositive adults who received one dose of Hib vaccine. Anti-polyribosylribitol phosphate (PRP) antibodies were measured at 0, 1, 3 and 12 months postimmunization by the Farr method. We demonstrate that all three vaccines are highly immunogenic and result in protective (>1.0 μg/ml) levels of antibody. Overall the anti-PRP antibody level was >1.0 μg/ml in 26% of patients preimmunization, 91% at both 1 and 3 months, and 79% at 12 months postvaccination. Comparison of responses to the three vaccines over time demonstrated differences in the mean geometric anti-PRP antibody level at 1 month ( p=0.03) and the 12 month time points ( p=0.03) with lower geometric mean levels in the HbNOMP group, though baseline differences in groups limit the interpretation of these findings. In a univariate analysis of baseline characteristics which predicted poor vaccine response, low total IgG2 levels preimmunization predicted a poor antibody response at 1 month ( p<0.01) and at 12 months ( p=0.05), while low CD4 T-cell count predicted poor response at 12 months ( p<0.01). We conclude that all three US licensed protein conjugate Hib vaccines are immunogenic in HIV-seropositive adults, and that baseline CD4 T-cell count and IgG2 levels predict the likelihood of antibody response to vaccine.

Haemophilus type B conjugate vaccine: postimmunization kinetics of IgM and IgG antibody responses in ten vaccinated children

A new Haemophilus type b conjugate vaccine coupling capsular polysaccharide of Haemophilus influenzae b to tetanus toxoid is available in France and other countries. We have studied the kinetics of the immune response in ten children aged 17 to 50 months during the 4 weeks after immunization with one dose of Haemophilus type b conjugate vaccine. Eight serum samples were collected from each child at day 0 (D0), D2, D4, D7, D10, D14, D21 and D28. An ELISA method has been used to discriminate between IgM and IgG classes of anti-polyribosylribitol phosphate antibodies. A high level of IgM appeared at D7 and persisted until D28. The increase in IgG was regular and progressive from D7.

Immunogenicity of Haemophilus influenzae Type b Conjugate Vaccine in Children with Congenital Asplenia

The immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugate vaccines in congenitally asplenic children is unknown. The short-term immunogenicity of the H. influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine was therefore assessed in 10 children with congenital asplenia by measuring antipolyribosyl-ribitol phosphate antibody titers. An excellent antibody response was seen in 9 children (mean geometric titer in responders after immunization 44.7 micrograms/mL; range, 2.59-402). The remaining child responded to a booster dose. Further studies are required to assess whether H. influenzae type b conjugate vaccines are immunogenic in infancy in the presence of congenital asplenia.

Distinct pattern of antibody reactivity with oligomeric or polymeric forms of the capsular polysaccharide of Haemophilus influenzae type b

The chain length of oligosaccharides required for antibody binding has been studied by using the capsular polysaccharide from Haemophilus influenzae type b or oligosaccharides derived from it. The concentration of competing antigens required to achieve a 50% inhibition of antibody binding by human polyclonal antisera in an in vitro competition enzyme-linked immunosorbent assay decreased progressively from greater than 10(-3) to 5 x 10(-7) M as the inhibiting saccharide chain length increased from 1 to 262 repeat units. Even small oligosaccharides (one or two repeat units) are potentially capable of competing to a significant level if a high enough concentration of saccharides is used. A similar pattern of reactivity was seen with a monoclonal anti-polyribosyl ribitol phosphate antibody, suggesting that the differences in the avidity of the antibody subpopulations in the polyclonal antisera do not contribute to the binding patterns observed. The binding reaction was specific as evaluated with pneumococcal saccharides. Furthermore, an oligosaccharide-protein conjugate binds antibody better than the free oligosaccharides do. Such a difference in binding was not observed between the polysaccharide and a polysaccharide-protein conjugate. Overall, the data suggest that identical epitopes are expressed by oligomeric and polymeric forms of the antigen and that a particularly more stable conformation in polysaccharides is preferred by antibodies. Covalent coupling of oligomers to protein increases the expression of stable conformation of epitopes. The data further suggest that this kind of antigenic analysis may be important for the design and synthesis of glycoconjugate vaccines.

Immunogenicity of Haemophilus Influenzae Type b Conjugate Vaccines in Infant Rhesus Monkeys

Two Haemophilus influenzae type b (Hib) polysaccharide-protein conjugate vaccines were evaluated for immunogenicity in eliciting anti-polyribosyl ribitol phosphate (PRP) antibodies in infant rhesus monkeys. Animals received intramuscular injections of either Hib polysaccharide (PRP)-meningococcal outer membrane protein complex or Hib oligosaccharide-CRM197 (HbOC) conjugate vaccines on d 0, 28, and 56. Because HbOC contains the CRM197 mutant diphtheria toxin from Corynebacterium diphtheriae as its protein carrier, the effect of simultaneous injection of diphtheria toxoid on the immunogenicity of HbOC also was evaluated by dividing monkeys vaccinated with HbOC into three groups: HbOC/saline, HbOC/diphtheria and tetanus toxoids, and HbOC/tetanus toxoid (coadministration of HbOC and other vaccine or placebo injected into the flank muscle of different legs). Infant monkeys vaccinated with the PRP-outer membrane protein complex conjugate responded with anti-PRP antibody after the first dose and showed booster responses after the second and third injections. In contrast, infant monkeys vaccinated with HbOC did not respond after three doses of HbOC/saline or HbOC/tetanus toxoid. However, two of three monkeys given concurrent injections of HbOC and diphtheria and tetanus toxoids did respond. The nonresponder monkey to three doses of HbOC and diphtheria and tetanus toxoids did respond to a subsequent injection with PRP-outer membrane protein complex. Thus, concomitant administration of diphtheria toxoid, a common vaccine for human infants, is necessary to elicit an anti-PRP antibody response to HbOC.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship of health-related variables to levels of anti-polyribosylribitol phosphate antibodies in adults

To identify adults who may be at risk for Haemophilus influenzae type b disease by virtue of low levels of antibody against the H. influenzae b capsule and who may thus benefit from receiving H. influenzae b vaccine, we correlated serum anticapsular antibody levels of 388 adult patients with 26 health-related variables, including 3 personal characteristics, 10 laboratory values, 4 drug use categories, and 8 disease categories. Steroid use was consistently associated with low levels of anticapsular antibody; associations were also found between low antibody levels and both non-Caucasian race and increasing age. However, less than 4% of the antibody variability could be attributed to these factors, and they were not predictive of low antibody levels. Thus, although H. influenzae b infections are seen in adults with predisposing medical conditions, on the basis of the present findings, use of the H. influenzae b vaccine in adults cannot be recommended.

1143 LABORATORY ASSESSMENT OF PROTECTION AGAINST H. INFLUENZAE TYPE B (Hib)

The protective level of anti-polyribosylribitol phosphate (PRP) antibodies has been estimated to be 0.15 to 1 μg/ml. An enzyme-linked immunosorbent assay (ELISA) to detect anti-PRP antibodies was used to test 20 cord sera treated with staphylococcal protein A to remove IgG. A seronegative range of <0.02 (delta optical density) was determined by adding 3 SD to the mean. 13/20 untreated cord sera were positive; 0/10 were seropositive by 7-14 months of age reflecting a loss of passively acquired antibody. 2/14 children 16-24 months of age were seropositive probably reflecting infection with Hib. 3/7 of the younger children were seropositive after a single dose of PRP conjugated to diphtheria toxoid (PRP-D) while all were positive after a booster dose. Following a single dose of PRP-D all 9 of the older group were seropositive while only 1/3 PRP recipients were positive. The ELISA value equivalent to 1 μg/ml of anti-PRP, was found in 4/7 younger vaccinees and 8/9 older vaccinees receiving PRP-D and only 1/4 older vaccinees receiving PRP. By defining the seronegative range it was possible to determine which vaccinees, who had lost maternal antibody and not experienced natural infection, had a T cell dependent (IgG) response. PRP-D appeared to be more effective in older than younger children and probably more effective than PRP (24/90 recipients have been tested). By comparing various methods of measuring immune response with protection, a more precise laboratory definition of “protection” can be developed.