Intranasal immunization with synthetic recombinant vaccine containing multiple epitopes of influenza virus.
The oligonucleotides coding for three epitopes (HA91-108, NP55-69, and NP 147-158) of influenza virus, stimulating B-cells, T-helper cells and cytotoxic T lymphocytes (CTLs), respectively, were previously employed for expressing each epitope in flagella that induced specific humoral and cellular immune responses. We have constructed new plasmids expressing all three epitopes as a single recombinant product. Two versions have been prepared-a longer one (Fla-HNN) comprising hybrid flagella containing the epitopes, and a shorter version (HNN). Immunization of BALB/c mice with either constructs induced significant humoral immune response against influenza virus. The mice immunized with these peptides also induced higher T-helper activity, including Th1 type-cytokine (IL-2 and IFN-gamma) release. In addition, the mice immunized with HNN peptide demonstrated significant protection against sublethal viral challenge. Furthermore, this vaccine fully protected mice from lethal challenge and enhanced their recovery process. Our results indicate that a single construct expressing multiple epitopes, which stimulate different arms of the immune system, might be an appropriate candidate when the synthetic recombinant vaccine approach is considered.
Jeon
Sung Ho
SH
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Ben-Yedidia
Tamar
T
Arnon
Ruth
R
D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay; D007111:Immunity, Cellular; D016056:Immunodominant Epitopes; D009980:Influenza A virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000276:immunology
D016056:Immunodominant Epitopes; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic