Antibacterial and antifungal vaccines based on synthetic oligosaccharides - Carbohydrate Chemistry: Chemical and Biological Approaches - page 572

Scheme 4
conjugated it to several proteins including TT. The conjugates induce a
protective immune response in mice. In a more recent study, Sp serotype
3 was chosen as a model for studying shorter synthetic oligosaccharides.
Conjugates of mono, di (1 unit), tri 12 and tetrasaccharide 13 (2 unit) to a
mutant of diphtheria toxin (CRM 197), 65 were obtained 66 and used for
immunization studies. As a result, the authors demonstrate that the tri-
and tetrasaccharide afford full protection of all mice from infection with
live Sp serotype 3 bacteria. Further studies with the use of different ad-
juvants and a trisaccharide conjugate confirm the high capacity of syn-
thetic oligosaccharides to induce antibodies with opsonofagocitic and
protective capacity in mice. 67 Considering the failure of the serotype 3 68
in multivalent Sp conjugate vaccines, further studies with synthetic
oligosaccharides could be of special interest.
2.4.2 Serotype 23F. The repeating unit 14 of this important com-
ponent of a multivalent Sp conjugate vaccine is composed of a
trisaccharide backbone with two branches at the central D -Gal; an a-
L -Rhamnose and glycerol-2-phosphate (Scheme 5). Immunization using
synthetic tetrasaccharide (15, 1RU) conjugated to keyhole lympet
hemocyanin (KLH) shows no response in mice and a strong anti-PS23F
IgG response in rabbits. The study 69 confirms that small oligosaccharide-
conjugates can induce anti-CPS antibodies with a relatively high opsonic
capacity. The divergence between the immune response among different
laboratory animals and humans is particularly evident for the RU of
Sp23F: excellent response in rabbits, absence of response in mice. In the
case of human serum of individuals immunized with the 23FCPS the
recognition was poorer than for rabbit serum.
2.4.3 Serogroup 6. The CPS of serotypes 6A (16) and 6B (17) have
closely related structures. Anti-6B antibodies are cross-protective to some
extent for 6A. 70 A new serotype 6C 18 was isolated recently 71 and has also
attracted much attention (Scheme 6). The serotype 6B-CRM 197 conjugate
is less immunogenic than the other CRM 197 conjugates in the 7-valent
Pneumococcal Conjugate Vaccine, Prevnar s . 72 In this context, the syn-
thesis of serotype 6B di-, tri-, and tetrasaccharide (19)-KLH-conjugates