Inmunogenicidad de conjugados de polisacárido de Neisseria meningitidis serogrupo C unido al toxoide tetánico por diferentes brazos espaciadores

Abstract

The development of polysaccharide-protein conjugate vaccines for
Haemophilus influenzae type b, which have proven to be efficacious in infants
and young children, has led to active development by a number of investigators
of conjugate vaccines for other diseases. The influence on immune response of
the structure of spacer arms used in N. meningitidis serogroup C polysaccharide
(MGCP)tetanus toxoid (TT) conjugate was evaluated in Balb/c mice. The IgG
anti-MGCP and IgG anti-TT elicited in serums of mice immunized with conjugates
and MGCP unconjugated, were evaluated by an ELISA method. The IgG
subclass (IgG1 and IgG2a) anti-MGCP elicited in serums of animals immunized
with conjugates and MGCP unconjugated, were also evaluated. 1,6-diaminohexane
(AH), 1,8-diaminooctane (AO), 6-aminohexanoic acid (AA) and adipic acid
dihydrazide (ADH) were used like spacer arms with different structure, linked to
MGCP and TT using carbodiimide-mediated coupling. All mice that were inoculated
with conjugates, showed high titles of IgG anti-MGCP, but the higher titles
were found in serums of mice immunized with conjugates with ADH as spacer
arm. In serum of mice immunized with conjugates with AO or ADH were detected
higher titles of IgG2a anti-MGCP than in mice immunized with MGCP
unconjugated, and the higher titles of IgG2a anti-MGCP were observed in sera of
mice immunized with conjugates with
ADH. Higher levels of anti-TT antibodies
were observed in sera of mice immunized
with conjugates than titles observed
in sera of mice immunized with
TT itself. As conclusion, it was obtained
that the immune response of conjugates
varied in dependence of chemical
structure of spacer arms used in the
link MGCP to TT, being higher when
it is used ADH.