Immunogenicity and safety of the Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine co-administered with human rotavirus, hepatitis A and 13-valent pneumococcal conjugate vaccines: results from a phase III, randomized, multicenter study in infants.

This phase III, open-label, randomized study (NCT01978093) evaluated the immunogenicity and safety of co-administered Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (Hib-MenCY-TT) with human rotavirus vaccine (HRV), hepatitis A vaccine (HAV) and 13-valent pneumococcal conjugate vaccine (PCV13). We randomized 600 infants (1:1) to receive 4 doses of Hib-MenCY-TT at 2, 4, 6 and 12-15 months of age or 3 doses of Hib vaccine conjugated to N. meningitidis outer membrane protein complex (Hib-OMP) at 2, 4 and 12-15 months of age.

Involvement of the iron regulatory protein from Eisenia andrei earthworms in the regulation of cellular iron homeostasis.

Iron homeostasis in cells is regulated by iron regulatory proteins (IRPs) that exist in different organisms. IRPs are cytosolic proteins that bind to iron-responsive elements (IREs) of the 5'- or 3'-untranslated regions (UTR) of mRNAs that encode many proteins involved in iron metabolism. In this study, we have cloned and described a new regulatory protein belonging to the family of IRPs from the earthworm Eisenia andrei (EaIRP).

Microbial environment affects innate immunity in two closely related earthworm species Eisenia andrei and Eisenia fetida.

Survival of earthworms in the environment depends on their ability to recognize and eliminate potential pathogens. This work is aimed to compare the innate defense mechanisms of two closely related earthworm species, Eisenia andrei and Eisenia fetida, that inhabit substantially different ecological niches. While E.

Molecular characterization of the iron binding protein ferritin in Eisenia andrei earthworms.

Ferritin is a storage protein that plays a key role in iron metabolism. In this study, we report on the sequence characterization of a ferritin-coding cDNA in Eisenia andrei earthworms isolated by RT-PCR using degenerated primers, and we suggest the presence of a putative IRE in the 5'-UTR of ferritin mRNA. The obtained ferritin sequence was compared with those of other animals showing sequence and structure homology in consensus sites, including the iron-responsive element (IRE) and ferroxidase centers.

Earthworm immunity.

Earthworms belonging to oligochaete annelids became a model for comparative immunologists in the early sixties with the publication of results from transplantation experiments that proved the existence of self/nonself recognition in earthworms. This initiated extensive studies on the earthworm immune mechanisms that evolved to prevent the invasion of pathogens. In the last four decades important cellular and humoral pathways were described and numerous biologically active compounds were characterized and often cloned.

Identification and cloning of an invertebrate-type lysozyme from Eisenia andrei.

Lysozyme is a widely distributed antimicrobial protein having specificity for cleaving the beta-(1,4)-glycosidic bond between N-acetylmuramic acid (NAM) and N-acetylglucosamine (GlcNAc) of peptidoglycan of the bacterial cell walls and thus efficiently contributes to protection against infections caused mainly by Gram-positive bacteria. In the present study, we assembled a full-length cDNA of a novel invertebrate-type lysozyme from Eisenia andrei earthworm (EALys) by RT-PCR and RACE system. The primary structure of EALys shares high homology with other invertebrate lysozymes; however the highest, 72% identity, was shown for the destabilase I isolated from medicinal leech.

Characterization, molecular cloning and localization of calreticulin in Eisenia fetida earthworms.

Calreticulin is a highly conserved calcium-binding protein affecting many cellular processes inside and outside of the endoplasmic reticulum (ER). It participates in the regulation of Ca(2+) homeostasis, acts as a chaperone and modulates gene transcription, integrin-mediated cell signalling as well as cell adhesion. Here we report on the sequence characterization of a calreticulin-coding cDNA of Eisenia fetida earthworms.

An invertebrate TNF functional analogue activates macrophages via lectin-saccharide interaction with ion channels.

The invertebrate pattern-recognition protein named coelomic cytolytic factor (CCF) and the mammalian cytokine tumor necrosis factor (TNF) share functional analogies that are based on a similar saccharide recognition specificity. In particular, CCF and TNF have been shown to interact with ion channels on the surface of vertebrate cells via N,N'-diacetylchitobiose lectin-like activity. In the present study, we show that CCF-induced membrane depolarization results in the release of TNF, IL-6 and nitric oxide (NO) by macrophages via nuclear factor-kappaB signaling.

Evidence for proteins involved in prophenoloxidase cascade Eisenia fetida earthworms.

The prophenoloxidase cascade represents one of the most important defense mechanisms in many invertebrates. Following the recognition of microbial saccharides by pattern recognition molecules, proteinases cleave inactive prophenoloxidase to its active form, phenoloxidase. Phenoloxidase is a key enzyme responsible for the catalysis of the melanization reaction.

Comparative study of the CCF-like pattern recognition protein in different Lumbricid species.

Coelomic fluid of the Lumbricid Eisenia fetida contains a 42-kDa pattern recognition protein named coelomic cytolytic factor (CCF) that binds microbial cell wall components and triggers the activation of the prophenoloxidase cascade, an important invertebrate defense pathway. Here we report on the sequence characterization of CCF-like molecules of other Lumbricids: Aporrectodea caliginosa, Aporrectodea icterica, Aporrectodea longa, Aporrectodea rosea, Dendrobaena veneta, Lumbricus rubellus and Lumbricus terrestris, and show that CCF from E. fetida has a broader saccharide-binding specificity, being the only one recognizing N,N'-diacetylchitobiose.

Relationship between hemolytic molecules in Eisenia fetida earthworms.

The coelomic fluid of the earthworm Eisenia fetida has been reported to contain a variety of proteins causing the lysis of red blood cells-EFAF (Eisenia fetida andrei factor), fetidin, lysenin, eiseniapore, and hemolysins isolated either from coelomic fluid (H1, H2, H3) or from cell lysate (CL(39) and CL(41)). We document the presence of two distinct genes with a high level of homology. These genes encode fetidin and lysenin but their level of expression differs in individual E.

Effect of experimental microbial challenge on the expression of defense molecules in Eisenia foetida earthworm.

Earthworms are able to protect themselves against invading pathogens due to efficient innate defense mechanisms. Currently, two types of antimicrobial factors including lysozyme-like molecule and factors with hemolytic activity, as well as a pattern recognition protein named coelomic cytolytic factor (CCF) have been identified in Eisenia foetida earthworms. However, the modulations of these defense molecules during in vivo immune response have not been addressed.