Development of VAX128, a recombinant hemagglutinin (HA) influenza-flagellin fusion vaccine with improved safety and immune response.

Background: We evaluated the safety and immunogenicity profiles of 3 novel influenza vaccine constructs consisting of the globular head of the HA1 domain of the Novel H1N1 genetically fused to the TLR5 ligand, flagellin. HA1 was fused to the C-terminus of flagellin in VAX128A, replaced the D3 domain of flagellin in VAX128B and was fused in both positions in VAX128C.

Methods: In a dose escalation trial, 112 healthy subjects 18-49 and 100 adults ≥65 years old were enrolled in a double blind, placebo controlled clinical trial at two centers.

Immunization of patients with rheumatoid arthritis with antitumor necrosis factor alpha therapy and methotrexate.

Purpose Of Review: The aim of this study is to highlight the recent findings on the use of methotrexate and/or TNFalpha-blockers in adult patients with rheumatoid arthritis and their effects on the immune response to various vaccines.

Recent Findings: Regarding influenza vaccination, methotrexate monotherapy is not associated with a decreased response, whereas the use of etanercept and infliximab in combination with methotrexate may cause lower titers and lower response rates. Concerning pneumococcal vaccination, methotrexate seems to impair responsiveness.

Influence of different immunoglobulin G preparations on phagocytosis of Pseudomonas aeruginosa by polymorphonuclear granulocytes.

Commercially available immunoglobulin products suitable for intravenous application in humans are made by enzymatic or chemical modification of the IgG molecule. In order to examine, to which extent in vitro biologic functions of the IgG molecule are preserved in such preparations, specific antipseudomonal IgG from the rabbit was modified according to some of these procedures. The opsonizing activity of the different IgG preparations was evaluated in an in vitro system measuring the phagocytosis of Pseudomonas aeruginosa by rabbit granulocytes.

In vitro and in vivo activities of different immunoglobulin G preparations from the rabbit against Enterobacteriaceae.

Specific rabbit IgG, prepared against three enterobacterial strains, was modified according to procedures used for the production of human IgG preparations suitable for intravenous infusion. The resulting products were examined for their in vitro opsonic and in vivo protective activity against the respective bacterial strains. A sulfonated IgG preparation (S-sIgG) and the enzymatically derived fragments F(ab')2 and Fab/Fc were opsonic in vitro and provided in vivo protection against lethal enterobacterial infection in mice.

Experimental Klebsiella septicemia in mice: treatment with specific antibodies from the rabbit alone and in combination with gentamicin.

Using a model of an experimental Klebsiella pneumoniae septicemia in mice, we examined the therapeutic effect of passively administered specific antibacterial antibodies from rabbits. Both specific IgM and IgG antibody proved to be therapeutically effective. However, the effect of IgG was markedly superior to that of IgM with regard both to the degree of protection and the time interval allowing efficient therapy after infection.