Chemistry Reference
In-Depth Information
A search for its epitope revealed
75
it to be a-
D
-Glcp(1-3)-a-L-Rhap, which
is present in the serogroup 6 PSs, as well as in serotype 19A PS. The
synthesis of the tetrasaccharide repeating units of 6A,
76
6B
77
and 6C,
78
and their BSA conjugates were accomplished. Preliminary studies with
the synthetic compounds confirm the recognition by Sp-specific rabbit
antiserum of serotypes 6A, 6B, and 6C, with significant cross-reactivity.
2.4.4 Serotype 14. Sp serotype 14 is one of the most important causes
of diseases in children worldwide. The capsular polysaccharide repeating
unit structure 20 is unusual for Sp. Fragments of the capsular poly-
saccharide from 1.4 to 150.0 kDa were obtained after N-deacetylation
followed by nitrous acid deamination.
79
Immunization of rabbits with
tetanus toxoid conjugates showed that at least 4 RU of Pn14PS were re-
quired to form an extended conformational epitope. This conformational
epitope was found to be essential for the induction of antibodies with
high opsonophagocytic activity. These results however were not con-
firmed by a very extensive work with synthetic oligosaccharide frag-
ments.
80
A series of 16 overlapping oligosaccharide fragments of Pn14PS
were synthesized
81-83
by a combined chemo-enzimatic approach to shed
more light on the required minimal epitope of Sp14 (Scheme 7).
Glycoconjugates with CRM
197
starting from a tri- and tetrasaccharide
(21) already induce anti-PS14 antibodies. The presence of a branch in the
structure was a requisite for the recognition of antibodies and for their
opsonophagocitic
84
activity. Mice
85
were immunized with the tetra-(21),
octa- and dodecasaccharide (22)CRM
197
conjugates (1,2 and 3 RU re-
spectively). The recognition as well as the phagocytic capacity was
similar among them, confirming than the conjugate 21 deserves further
study and could be an excellent candidate for the development of a
vaccine.
Scheme 7
Search WWH ::
Custom Search