Blocking by Anti‐Idiotypic Antibodies of Monoclonal Antibody‐Mediated Protection Against Lethal Semliki Forest Virus in Mice

Abstract

Semliki Forest virus-(SEV) neutralizing monoclonal antibodies (MoAbs), produced after fusion of spleen cells from BALB/c mice and myeloma cell line P3-X63-AG8. 653 or SP2/0, were used for anti-idiotypic immunization of female BALB/c mice. Two intracutaneous immunizations (2 x 40 micrograms per animal), 3 weeks apart, with keyhole limpet haemocyanin-conjugated MoAbs mixed with the saponin Quil A were sufficient to induce high levels of anti-idiotypic antibodies in the circulation of these mice with the capacity to block specifically in vitro MoAb-mediated virus neutralization. Anti-idiotypic antibodies against SFV-neutralizing MoAbs, either passively transferred or actively acquired by immunization, are also able to abrogate (specifically) passive immunity, mediated by critical protective doses of MoAb, in mice against infection with a lethal strain of SFV. Furthermore we confirmed by intervention with anti-idiotypic serum in vivo that an SFV-neutralizing MoAb exerts its greatest protective effect during the first 2 days of infection.

A protective monoclonal anti-idiotypic vaccine to lethal Semliki Forest virus infection in BALB/c mice

“…A prerequisite for the detection of ab2 MAbs is adequate immunization of mice whose spleens are destined for fusion. In agreement with earlier reports (15,16), we demonstrate in the present study that an immunization protocol with KLHcoupled abl MAb and Quil A is very useful for induction of ab2 antibodies (Fig. 1).…”

“…Blood was obtained on days 7 (n = 2), 11 (n = 2), 15 (n = 2), 18 (n = 2), 21 (n = 2), 24 (n = 4), 28 (n = 2), and 35 (n = 2). The last two mice received on day 35 a booster immunization similar to the primary immunization.…”

“…In the present study we used a solid-phase independent detection method for ab2 MAb, namely, neutralization inhibition EIA (NI-EIA). With this method, ab2 antibodies are detected by their capacity to block abl MAb-mediated neutralization of Semliki Forest virus (SFV) as described previously (15,16). Moreover, the induction of ab2 serum antibodies to SFV-neutralizing abl MAbs was greatly facilitated by the use of the adjuvant Quil A (13).…”

“…Moreover, the induction of ab2 serum antibodies to SFV-neutralizing abl MAbs was greatly facilitated by the use of the adjuvant Quil A (13). High levels of neutralization blocking ab2 antibodies were evoked upon intracutaneous and subcutaneous injection of BALB/c mice with SFV-neutralizing MAb chemically coupled to keyhole limpet hemocyanin (KLH) and combined with Quil A (15). We suppose that ab213 MAbs are neutralization-blocking antibodies, because they bind to the antigen combining site (paratope).…”

Preparation, characterization, and immunogenicity of meningococcal immunotype L2 and L3,7,9 phosphoethanolamine group-containing oligosaccharide-protein conjugates

“…A enhances the immune response against polysaccharide-protein conjugates as well as OS-protein conjugates (6a, 33). It is currently used for the preparation of anti-idiotypic antibodies against a number of antigens (25,26). Most of these studies, however, are performed in mice, and limited data are available about the adjuvant effects of Quil A in rabbits (31).…”