Experimental infection and protection against ... - TI Pharma

A saturation of antibody avidity and concentration induced by malaria vaccine
candidate Apical Membrane Antigen 1
thus establish an equilibrium depending on their competition for common
resources, of which antigen is only one [17]. The availability of other resources,
such as growth factors, interleukins and the presence of adhesion molecules
may provide critical advantage preserving diversity and preventing dominance of
one B-cell pool [18]. This is an interesting hypothesis, because it suggests that
possible addition of resources to the antigen (such as cytokine adjuvants) would
offer an opportunity to increase the specific B-cell population beyond the
current maximum.
Few sera did not reach the saturated level, particularly in the Alhydrogel®
adjuvanted group. We hypothesize that the antibody response in these sera may
not have undergone full maturation and have not (yet) reached a maximum
fraction of bound antigen. Similarly, allergen-specific IgE from atopic children
also lacked a negative relationship between concentration and avidity [19],
whereas this was apparent for the more matured antibody responses in adults
[16].
These data are particularly relevant for vaccine development, since the avidity of
antibodies may determine susceptibility to diseases such as the Respiratory
Syncytial virus or meningococcal disease [20-22]. For AMA1 antibodies, we
found a relation between in vitro parasite growth inhibition and antibody
concentration, but not avidity. Caution should be taken, however, when
concluding that the functionality of AMA1 antibodies in vitro seems to be
governed primarily by concentration of antibodies, as epitope functionality has
not been taken into account in this study. Particularly PfAMA1 domain I and
domain II antibodies are thought to harbour the major targets for inhibitory
responses [7]. Moreover, the results of in vitro growth inhibition so far do not
correlate with in vivo susceptibility [23].
In conclusion, our data illustrate an inverse relation between concentration and
avidity, that becomes saturated at a maximum, constant capacity to bind
antigen. Any increase in antibody concentration at this saturated level will be
balanced by a decrease in antibody avidity. The appreciation of a saturated
antibody response may be crucial for the future development of PfAMA1
vaccine, since it provides guidance to the search for more effective antigens,
adjuvants or delivery platforms.
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