Intranasal coinfection model allows for assessment of protein vaccines against nontypeable Haemophilus influenzae in mice.

PURPOSE: Nontypeable Haemophilus influenzae (NTHi) is a commensal in the human nasopharynx and the cause of pneumonia, meningitis, sinusitis, acute exacerbations of chronic obstructive pulmonary disease and acute otitis media (AOM). AOM is the most common ailment for which antibiotics are prescribed in the United States. With the emergence of new strains of antibiotic-resistant bacteria, finding an effective and broad coverage vaccine to protect against AOM-causing pathogens has become a priority. Mouse models are a cost-effective and efficient way to help determine vaccine efficacy. Here, we describe an NTHi AOM model in C57BL/6J mice, which also utilizes a mouse-adapted H1N1 influenza virus to mimic human coinfection. METHODOLOGY: We tested our coinfection model using a protein vaccine formulation containing protein D, a well-studied NTHi vaccine candidate that can be found in the 10-valent Streptococcus pneumoniae conjugate vaccine. We verified the usefulness of our mouse model by comparing bacterial loads in the nose and ear between protein D-vaccinated and control mice. RESULTS: While there was no measurable difference in nasal bacterial loads, we did detect significant differences in the bacterial loads of ear washes and ear bullae between vaccinated and control mice. CONCLUSION: The results from this study suggest that our NTHi AOM coinfection model is useful for assessing protein vaccines.

The 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) coadministered with DTPw-HBV/Hib and poliovirus vaccines: assessment of immunogenicity.

BACKGROUND: Immunogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) was evaluated when coadministered with DTPw-HBV/Hib and OPV at 6, 10, and 14 weeks of age in the Philippines, or with DTPw-HBV/Hib and IPV at 2, 4, and 6 months of age in Poland. METHODS: In this double-blind, controlled study (107007/NCT00344318), 400 Filipino and 406 Polish infants 6 to 12 weeks of age were randomized (3:1) to receive either PHiD-CV or the 7-valent pneumococcal conjugate vaccine (7vCRM). Immune responses were assessed 1 month post-dose III. RESULTS: Percentages of infants with anti-pneumococcal antibody concentrations >or=0.2 microg/mL (GSK's 22F-inhibition ELISA) were within the same range for both pneumococcal conjugate vaccine groups, with the exception of serotypes 6B and 23F for which lower percentages were observed in the PHiD-CV group in Poland. At least 98.2% of PHiD-CV vaccinees had antibody concentrations >or=0.2 microg/mL against pneumococcal serotypes 1, 5, and 7F. In both countries, anti-pneumococcal antibody geometric mean concentrations against serotypes 18C and 19F were higher in the PHiD-CV group than in the 7vCRM group. Antibody geometric mean concentrations for most of the other common serotypes were within the same range for both groups in the Philippines and were lower in the PHiD-CV group in Poland. Functional responses (opsonophagocytic activity [OPA]) were observed for all vaccine serotypes in both countries. CONCLUSIONS: PHiD-CV was immunogenic against each of the 10 pneumococcal vaccine serotypes when coadministered with DTPw-HBV/Hib and poliovirus vaccines.

[Clinical aspects of prenatal prevention of rhesus incompatibility]. / Klinische Aspekte der antenatalen Rhesus-Prophylaxe.

The postnatal treatment with anti-D immunoglobulin to prevent rhesus sensitization is successful in about 90% of all rhesus-negative mothers at risk. Failures derive mostly from large fetomaternal hemorrhages during the last months of pregnancy. Studies from Canada, Great Britain and Sweden have shown that the injection of an additional dosage of anti-D during the 28th to 34th week of pregnancy results in a further 90% reduction of the failure rate. Although there is only a limited number of cases of hemolytic diseases in the newborn, the cost-effect ratio of this prophylactic treatment calculated for the Federal Republic of Germany shows not only a medical but also an economic benefit.

Assessment of antigen-specific receptor function of surface immunoglobulin M and D with identical hapten specificity.

Monoclonal B-cell lines expressing antigen-specific surface IgM or IgD were established by transferring the genes encoding immunoglobulin heavy (mu or delta) and light (kappa) chains specific for the hapten 2,4,6-trinitrophenyl (TNP) into a B-cell lymphoma line. Two IgMTNP and two IgDTNP transformants were selected on the basis of similar levels of anti-TNP idiotype expression by flow microfluorimetric analysis. The IgMTNP and IgDTNP transformants were compared in quantitative assays for their ability to bind TNP-carrier and present TNP-carrier to carrier-specific T cells. Our results indicate that IgMTNP and IgDTNP transformants have an equal capacity to bind and present specific antigen. Thus surface IgM and IgD, when present in equivalent amounts, function similarly as antigen receptors.