DEVELOPMENT OF HUMAN-ANTIBODIES AGAINST LINEAR ANTIGENIC AND IMMUNOGENIC REGIONS OF RESPIRATORY SYNCYTIAL VIRUS (RSV) NUCLEOCAPSID AND PHOSPHO-PROTEINS SHOWS THE SITE-DIRECTED CHARACTERISTICS

Citation
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
Citations number
32
Categorie Soggetti
Virology
ISSN journal
13866532
Volume
11
Issue
2
Year of publication
1998
Pages
137 - 147
Database
ISI
SICI code
1386-6532(1998)11:2<137:DOHALA>2.0.ZU;2-O
Abstract
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.