A hemagglutinin-derived peptide-vaccine ignored by virus-neutralizing passive antibodies, protects against murine measles encephalitis.
The neutralizing and protective monoclonal antibody BH47 defines the sequential epitope H236-255 of the measles virus hemagglutinin protein (MV-H). The objective of this study was to design peptides combining this B cell epitope (BCE) with different T cell epitopes (TCE) to obtain protective immunity. Most TTB peptides based on the 15mer BCE H236-250 induced MV-crossreactive antibodies, but only certain TCE induced virus neutralizing antibodies. The shortest BCE required for MV-reactivity and -neutralization was the 8mer H243-250 containing residue R243 implicated in CD46 down-regulation. Sera obtained after immunization with the TTB peptide containing the MV-derived TCE F421-435 protected mice against a lethal challenge with a neuro-adapted MV strain. Our results further demonstrate that this TTB peptide is fully immunogenic, even in the presence of protective levels of pre-existing MV-specific antibodies, suggesting that subunit vaccines based on such peptides could potentially be used to immunize infants in the presence of persisting maternal antibodies. It is therefore interesting that neutralizing antibodies were also obtained with a TTB peptide comprising a human promiscuous TCE (tt830). However, our results also emphasize the need to test sera induced with epitope-based vaccines against different virus strains, in particular if the epitope is not fully conserved.
Laboratoire National de Santé, C.P.M., Department of Immunology, Luxembourg, Luxembourg.
K C
KC
El Kasmi
D
D
Theisen
N H
NH
Brons
W
W
Ammerlaan
M
M
Klingele
A T
AT
Truong
C P
CP
Muller
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000918:Antibody Specificity; D018792:Encephalitis, Viral / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006389:Hemagglutinins, Viral / Q000276:immunology; D007106:Immune Sera / Q000276:immunology; D007116:Immunization, Passive; D007274:Injections, Intraperitoneal; D008297:Male; D008457:Measles / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control*; D008459:Measles virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D010455:Peptides / Q000276:immunology; D015996:Survival Rate; D014765:Viral Vaccines / Q000276:immunology
D000911:Antibodies, Monoclonal; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D006389:Hemagglutinins, Viral; D007106:Immune Sera; D010455:Peptides; D014765:Viral Vaccines