Carbohydrate Antigens
antigens. The time required to develop
full responsiveness to TI stimulations dif-
fers signiFcantly among antigenic systems
studied. In mice, antibody responses to
TI-I antigens (LPS and other) and pro-
tein antigens reach adult levels within 1 to
2 weeks; antibodies to TI-II antigens can be
detected only at 2 to 3 weeks. ±or pneumo-
coccal polysaccharides SSS-III and dextran
B1355S, full development of the antibody
response is not reached until 4 weeks;
with polysaccharides levan and
dextran, 7 and 13 weeks respectively are
needed. In humans, children younger than
18 months fail to respond to microbial
polysaccharides or produce antibodies at
levels too low to be protective. Such poor
responsiveness generally lasts until 5 years
of age. Thus, there is a period when ma-
ternally derived protective antibodies have
declined; yet the age-related development
of immunity to bacterial infection remains
immature. Pathogens causing severe prob-
lems during this high-risk period have
long posed the need for developing efF-
cient vaccines.
age delay in antipolysaccharide responses
is still poorly understood. It has been
illustrated that two distinct B-cell lin-
eages/subtypes – B-1 and conventional B-
cell – have different kinetics of B-cell de-
velopment and functional maturation. It
is interesting to see whether the delayed
maturation of antibody responses to TI
antigens coincides with B-1 or B-2 cell
maturation. B-1 cell lineages (B-1a and B-
1b) develop earlier than do conventional
B-cells. By 4 weeks after birth, the mouse
B-1 cell population approaches adult size
and is able to mount a normal level of anti-
body response. Conventional B-cells reach
maximal levels at 12 to 14 weeks of age.
By comparing the kinetics of B-cell de-
velopment and the timing of maturation
of anti-TI antigen responses, it is clear
that the delayed ontogeny of antibody re-
sponse to some, but not all TI antigens,
may be attributed to the time required for
B-1 cell maturation.
was successfully developed to improve
childhood vaccination. Several important
molecular events elicited by T-dependent
antigens are lacking in the polysaccharide
induced antibody responses, including
memory cell induction, afFnity matura-
tion, and Ig H-chain class switching to
IgGs. These events may occur in GCs of
the peripheral lymphoid organs during
T-dependent immune responses. Thus,
efforts have been made to convert carbo-
hydrate antigens into T-dependent anti-
gens. Studies with T-dependent forms
6) dextran, made by coupling
isomaltose oligosaccharides to protein car-
riers, experimentally support this strategy.
This conversion resulted in a signiFcant
6) dextran was obtained. With
native dextran (TI-II), mouse antibody re-
sponses reach adult levels in about 12 to
13 weeks; with the T-dependent form, the
peak is at 3 to 4 weeks. V region sequence
data and combining site mapping estab-
lished that the T-dependent repertoire
of anti-
6) dextran differs from the
T-independent repertoire, indicating that
distinct B-cell populations were elicited by
the T-dependent conjugates.
Robbins and Schneerson (1990) intro-
duced the conjugate strategy for human
vaccination. By coupling puriFed capsular
polysaccharides of
Haemophilus influenzae
B with tetanus toxoid, the Frst polysac-
charide–protein conjugate against this
bacterium was made. This conjugate vac-
cine has been applied in over 40 countries
and is included in the Extended Program
on Immunization of the World Health
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