Biomedical Engineering Reference
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cytoplasmatic domain. 10 The ectodomain presents 16 conserved cysteine
residues, which are responsible for stabilisation via intramolecular disulphide
bridges that seem essential for inducing an antibody response which could
inhibit parasite development. 11 Because of its participation in the invasion
process, AMA-1 has been suggested as candidate for a vaccine against
Plasmodium pre-erythrocytic blood stages 12 ; in other words, it has shown the
ability to act as a target of antibodies that prevent parasites from invading red
blood cells in vitro and to induce protective immunity against challenge with
parasites in several animal models ( in vivo ). 13 To that purpose, a promising
malaria peptide from the AMA-1 protein sequence was conjugated to multi-
walled CNTs (MWCNTs) and injected in mice. Unfortunately, the CNT-peptide
complex did not improve the antibody titers as much as the free peptide did,
most probably because of other factors (e.g., surface charges) that might have
promoted the co-adsorption of some complement system's down-regulating
agents (e.g., factor H). 14 At the same time, the use of acetylated CNTs (which
are uncharged nanotubes without peptide sequences attached) did not
trigger any signiicant values for antibodies, thereby demonstrating that the
immune response was peptide-speciic and that CNTs were not intrinsically
immunogenic. 5,7
As regards the protection of treated mice against a challenging dose
of antigen, three mice (out of 30 mice) became protected: mice 7 and
9 from the group treated only with the peptide and mouse 23 from the
CNT-peptide conjugate group. Interestingly, the protection conferred to
the animals was not correlated to the antibody (Ab) titers produced, thus
decreasing the relevance of the higher Ab titers reported above with the
treatment of peptide alone. In fact some mice presented high antibody
titers but became infected following challenge with Plasmodium berghei .
On the contrary, mice 9 and 23 became protected against infection and
presented lower antibody levels (Figs. 4a and 4b). Mouse 7 presented a
good antibody level and became protected (Fig. 4a), indicating that both ine
a
b
Figure 4.4 Immunised mice sera antibody titers: (a) mice immunised with the 21267
peptide alone; (b) mice immunised with the CNT-peptide 21267 complex. Reproduced
from Yandara et al. 8 with permission.
 
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