Protection against measles virus-induced encephalitis by anti-mimotope antibodies: the role of antibody affinity.
Synthetic peptides mimicking a conformational B-cell epitope (M2) of the measles virus fusion protein (MVF) were used for the immunization of BALB/c mice and the anti-peptide and anti-virus antibody titers induced were compared. Of the panel of tested peptides, a chimeric peptide consisting of two copies of a T-helper epitope (residues 288-302 of MVF) and one copy of the mimotope M2 (TTM2) and a multiple antigen peptide with eight copies of M2 (MAP-M2) induced the highest titers of anti-M2 and anti-MV antibodies. Furthermore, peptides TTM2 and MAP-M2 induced antibodies with highest affinity for the mimotope and highest avidity for measles virus. Immunization with the MAP-M2 construct induced high titers of high-affinity anti-M2 antibody despite the absence of a T-helper epitope, and lymphocyte proliferation data suggest that the addition of M2 to the MAP resulted in the generation of a structure capable of stimulating T-cell help. Sera with anti-M2 reactivity were pooled according to affinity values for binding to M2, and high- and low-affinity pools were tested for their ability to prevent MV-induced encephalitis in a mouse model. The high-affinity serum pool conferred protection in 100% of mice, whereas the lower affinity pool conferred protection to only 50% of animals. These results indicate the potential of mimotopes for use as synthetic peptide immunogens and highlight the importance of designing vaccines to induce antibodies of high affinity.
Olszewska
W
W
The Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, United Kingdom.
Obeid
O E
OE
Steward
M W
MW
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000276:immunology*; D000915:Antibody Affinity / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D001921:Brain / Q000821:virology; D018792:Encephalitis, Viral / Q000276:immunology* / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007116:Immunization, Passive; D008213:Lymphocyte Activation / Q000276:immunology; D008458:Measles Vaccine / Q000138:chemical synthesis / Q000276:immunology; D008459:Measles virus / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000821:virology; D014614:Vaccines, Synthetic / Q000276:immunology; D014760:Viral Fusion Proteins / Q000276:immunology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D008458:Measles Vaccine; D010446:Peptide Fragments; D014614:Vaccines, Synthetic; D014760:Viral Fusion Proteins