A protective monoclonal anti-idiotypic vaccine to lethal Semliki Forest virus infection in BALB/c mice.
Two monoclonal anti-idiotypic antibodies (ab2 MAbs), designated 1.13A112 (immunoglobulin G type 2a [IgG2a]) and 1.13A321 (IgG1), were prepared against Semliki Forest virus (SFV)-neutralizing ab1 MAb UM 1.13. They were identified in hybridoma supernatant fluid by their capacity to block UM 1.13-mediated neutralization of SFV. Although the neutralization-blocking capacities of the ab2 MAbs did not differ, only 1.13A321 evoked SFV-neutralizing ab3 antibodies upon intracutaneous and subcutaneous immunization of BALB/c mice with 1.13A321 chemically cross-linked to keyhole limpet hemocyanin and combined with the adjuvant Quil A. SFV-neutralizing ab3 antibodies appeared in serum within 10 days after primary immunization, and neutralizing antibody titers could be as high as 1/1,000 at day 35. All mice who had developed SFV-neutralizing antibodies upon anti-idiotypic immunization survived an otherwise lethal challenge with virulent SFV. However, induction of SFV-neutralizing ab3 antibodies by ab2 MAb 1.13A321 proved to be genetically restricted to BALB/c mice; even haplotype-identical (H-2d) DBA/2 mice did not respond, and consequently those animals died after infection with virulent SFV.
Oosterlaken
T A
TA
Institute for Molecular Biology and Medical Biotechnology, Medical School, University of Utrecht, The Netherlands.
Harmsen
M
M
Jhagjhoor-Singh
S S
SS
Ekstijn
G L
GL
Kraaijeveld
C A
CA
Snippe
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000917:Antibody Formation; D005260:Female; D007124:Immunoenzyme Techniques; D007130:Immunoglobulin Idiotypes / Q000032:analysis / Q000276:immunology*; D007739:L Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009500:Neutralization Tests; D012672:Semliki forest virus; D013045:Species Specificity; D014036:Togaviridae Infections / Q000276:immunology* / Q000517:prevention & control; D014765:Viral Vaccines / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D007130:Immunoglobulin Idiotypes; D014765:Viral Vaccines