Chemistry Reference
In-Depth Information
regulate immune response; (2) CD8
þ
cytotoxic T cells (CTL) that kill cells
infected by viruses and other intracellular pathogens. B Lymphocytes
produce antibodies in response to antigens and antibodies bind to anti-
gens to neutralise them or help to destruction between microorganisms.
Nowadays, adjuvants are used to accomplish two main objectives: as
carriers for the antigen and as stimuli to the immune system. Literature
data show that a variety of glycolipids such as lipid A analogues, a-
galactosyl ceramides and complex saponins have been studied for that
purpose
80
but more recently, increasing attention has been directed to the
development of archaeal glycolipids that appear to be at least relatively safe
and inexpensive in comparison with other complex glycolipids. Within this
context, this section will essentially focus on the recent developments of
natural or synthetic archaeolipids for applications in archaeosome for-
mulations and in their applications as vaccine delivery systems.
Archaeosome formulations can be used as ecient carriers for
antigens and antigens promoting antigen-specific, humoral and cell-
mediated immune responses, in addition to antigen-specific mucosal
immune responses in the vaccinated hosts.
4.1 Lipid structures of archaeosome components
As mentioned in section 2.6, archaeosomes are nanosized vesicles,
composed of lipids found in archaea and constitute a novel family of
liposomes that give proof of higher stability to harsh conditions in
comparison to conventional liposomes.
43
The definition of archaeo-
somes also includes those made with synthetically derived lipids that
have the unique structural characteristics of natural lipids, for example:
(1) regularly branched phytanyl chains linked through ether bonds to sn-
2,3 carbons of glycerol; (2) monopolar archaeol (diether) lipids and/or
bipolar tetraether lipids linked to two glycerol entities in an antiparallel
manner (caldarchaeol) or in a parallel manner (isochaldarcheol);
81
(3)
neutral, negatively charged or zwitterionic unusual polar heads (Fig. 28).
A particularly attractive feature concerns the increasing proportion of
cyclopentane rings in the core of thermoacidophilic lipids with increas-
ing environmental temperature.
82
Indeed, the presence of cyclopentane
rings are supposed to fine-tune the rigidity of the membrane in response
to the growing temperature of the microorganisms.
83
The polar head groups found in natural lipids from archaea lipid ex-
tracts are generally highly sensitive to acidic hydrolysis and the extraction
methods used to isolate the hydroxylated archaeol (Fig. 28: R
1
¼
OH); cal-
darchaeol (Fig. 28: R
2
¼
R
3
¼
OH) and isocaldarchaeol (Fig. 28: R
2
¼
R
3
¼
OH)
respectively. Several research groups have taken advantage of these free
hydroxyl groups to chemically modify natural lipid structures by intro-
ducing new polar head groups. Of particular interest are the results pre-
sented by Sprott et al.
9,80,84,85
where they demonstrated that the adjuvant
potential of archaeal synthetic glycolipid mimetics critically depends on (1)
the structure of the glycol head group structures, and (2) the number of
sugar units attached to the sn-1 position of archaeol. The results show that
a week cytotoxic T-lymphocyte (CTL) adjuvant consisting of DPPG/Chol
liposomes being converted into a highly ecient adjuvant by the addition
Search WWH ::
Custom Search