DEVELOPMENT OF HUMAN-ANTIBODIES AGAINST LINEAR ANTIGENIC AND IMMUNOGENIC REGIONS OF RESPIRATORY SYNCYTIAL VIRUS (RSV) NUCLEOCAPSID AND PHOSPHO-PROTEINS SHOWS THE SITE-DIRECTED CHARACTERISTICS
Iv. Leonova et al., DEVELOPMENT OF HUMAN-ANTIBODIES AGAINST LINEAR ANTIGENIC AND IMMUNOGENIC REGIONS OF RESPIRATORY SYNCYTIAL VIRUS (RSV) NUCLEOCAPSID AND PHOSPHO-PROTEINS SHOWS THE SITE-DIRECTED CHARACTERISTICS, JOURNAL OF CLINICAL VIROLOGY, 11(2), 1998, pp. 137-147
Background: The successful development of an RSV vaccine requires a be
tter understanding of the pathogenesis of primary infection, susceptib
ility to reinfection, and the immunopathology of enhanced illness in c
hildren immunized with a non-replicating RSV candidate vaccine. The ex
act role of different immune parameters in RSV pathogenesis remains co
ntroversial. Objectives: To study the contribution of antibodies direc
ted to the linear antigenic and immunogenic regions of the N and P pro
teins in the titer rise and avidity maturation of total anti-RSV antib
odies. Study design: The occurrence of antibodies directed against thr
ee linear antigenic and immunogenic regions in each of the nucleocapsi
d (N): N3 (Thr(11) to Gly(30)), N25 (Ser(231) to Ala(250)) and N39 (Th
r(371) to Leu(391)), and the phospho-(P) proteins of respiratory syncy
tial virus (RSV), subgroup A: P49 (Pro(91) to Asp(110)), P56 (Ser(161)
to Lys(180)) and P62 (Glu(221) to Phe(241)), were analyzed in ELISA w
ith (a) 32 paired sera from humans with recent or previous RSV subgrou
p A and/or B infection diagnosed by conventional ELISA, detection of a
ntigen in nasopharyngeal aspirates and measurement of antibody avidity
change; and (b) 40 RSV antibody-positive sera (HCS) obtained from pat
ients during their convalescence from RSV infection and possessing cle
arly demonstrable titers of RSV IgG in conventional enzyme immunoassay
s (EIA) based on whole RSV antigen. Results: The titer rise of antibod
ies directed to the combined three peptides representing the RSV N pro
tein was well correlated with the rise in anti-RSV antibodies measured
in whole antigen ELISA. Surprisingly, the rise in antibodies against
a truncated main C-terminal epitope (Gln(381) to Leu(391)) of the N pr
otein (represented by subgroup A specific sequence of the N39/1 peptid
e) was inversely correlated with the titer rise of total anti-RSV anti
bodies. The titer rise of antibodies to the C-terminal linear site of
the RSV N (N39/1) protein was subgroup-specific during the course of p
rimary RSV infection. A titer rise in antibodies to the C-terminal lin
ear sites of RSV N (i.e. N39/1) and P (P62) proteins had a dominating
appearance in sera from newborn infants (6-7 months) and from patients
with RSV reinfections. Anti-RSV antibody titers of late convalescent
sera correlated with the titers of antibodies directed to the C-termin
al linear site of RSV P (P62) protein. The avidity maturation of the a
nti-RSV immune response followed the titer rise of anti-P62 antibodies
during the course of primary or secondary RSV infection. (C) 1998 Els
evier Science B.V. All rights reserved.