Pattern recognition receptors: doubling up for the innate immune response.

Minimal structural requirements for adjuvant activity of bacterial peptidoglycan derivatives.

The problem with pure recombinant or synthetic antigens used in modern day vaccines is that they are generally far less immunogenic than older style live or killed whole organism vaccines. This has created a major need for improved and more powerful adjuvants for use in these vaccines. With few exceptions, alum remains the sole adjuvant approved for human use in the majority of countries worldwide. Although alum is able to induce a good antibody (Th2) response, it has little capacity to stimulate cellular (Th1) immune responses which are so important for protection against many pathogens. In addition, alum has the potential to cause severe local and systemic side-effects including sterile abscesses, eosinophilia and myofascitis, although fortunately most of the more serious side-effects are relatively rare. There is also community concern regarding the possible role of aluminium in neurodegenerative diseases such as Alzheimer's disease. Consequently, there is a major unmet need for safer and more effective adjuvants suitable for human use. In particular, there is demand for safe and non-toxic adjuvants able to stimulate cellular (Th1) immunity. Other needs in light of new vaccine technologies are adjuvants suitable for use with mucosally-delivered vaccines, DNA vaccines, cancer and autoimmunity vaccines. Each of these areas are highly specialized with their own unique needs in respect of suitable adjuvant technology. This paper reviews the state of the art in the adjuvant field, explores future directions of adjuvant development and finally examines some of the impediments and barriers to development and registration of new human adjuvants.

Vaccine adjuvants: current state and future trends.

Distribution of the histaminergic neuron system in the central nervous system of rats; a fluorescent immunohistochemical analysis with histidine decarboxylase as a marker.

Publisher Summary This chapter discusses the analysis of the chemical composition and primary structure of the murein. Murein (peptidoglycan, mucopeptide) is the main cell wall polymer of eubacteria and is common to both Gram-negative and Gram-positive bacteria. There are only a few prokaryotic organisms, such as mycoplasmas and archaebacteria, which lack murein. The glycan moiety is rather uniform and shows only a few variations such as O-acetylation or O-phosphorylation or the exceptional absence of peptide substituents. The peptide moiety of the murein shows, in contrast to the glycan part, a considerable variation. Extensive investigation of the chemical structure of murein has demonstrated the existence of almost 100 different variations of the peptide moiety. Depending on the mode of cross-linking two main groups of murein, named A and B, have been distinguished. The different structure of cell walls of Gram-positive and Gram-negative bacteria necessitates discrete methods for preparing cell walls. The cell walls of Gram-positive bacteria reveal in profile one thick and more or less homogeneous layer, whereas Gram-negative bacteria have thinner, but distinctly layered cell walls with an outer membrane resembling the cytoplasmic membrane in profile.

5 Analysis of the Chemical Composition and Primary Structure of Murein

Adjuvant activity of monomeric bacterial cell wall peptidoglycans.

Aus n-acyl-muraminsaeurederivaten gebildete adjuvanzien und diese enthaltende impfstoffe

A vaccine compsn. contains an immunogenic agent and an adjuvant comprising a monomer (or oligomeric deriv.) contg. the N-acyl-muramic acid gp. in which the acyl gp. is glycolyl or acetyl, and a peptide chain comprising 2-8 amino acids. The first of the amino acids, bonded to the N-acyl muramic acid, comprises alanine, serine or glycine and the second comprises glutamic acid or aspartic acid. The adjuvants are esp. effective for stimulating immune response, to immunise man and warm blodded animals against bacterial, viral and parasitic infections and against tissue antigens of normal or pathologic orign esp. tumours.

Farielle Ellouz

Papers

Minimal structural requirements for adjuvant activity of bacterial peptidoglycan derivatives.

Adjuvant activity of monomeric bacterial cell wall peptidoglycans.

Aus n-acyl-muraminsaeurederivaten gebildete adjuvanzien und diese enthaltende impfstoffe

Vaccine compsns. - contg. N-acyl muramic acid deriv. as adjuvant

adjuvants and formed of n-acyl-muraminsaeurederivaten vaccines containing