A Dual-Type L2 11-88 Peptide from HPV Types 16/18 Formulated in Montanide ISA 720 Induced Strong and Balanced Th1/Th2 Immune Responses, Associated with High Titers of Broad Spectrum Cross-Reactive Antibodies in Vaccinated Mice

作者：Khiavi Farhad Motavalli; Arashkia Arash; Golkar Majid; Nasimi Maryam; Roohvand Farzin; Azadmanesh Kayhan

来源：Journal of Immunology Research, 2018, 2018: 9464186.

DOI：10.1155/2018/9464186

<jats:p><jats:italic>E. coli</jats:italic>-derived concatenated, multitype L2-conserved epitopes of human papillomavirus (HPV) L2 protein might represent a less expensive and pan-type vaccine alternative (compared to type-specific HPV L1 virus-like particles), if stable protein expression and strong immunogenicity features could be met. Herein, three dual-type- (DT-) HPV L2 fusion peptides comprising the three head-to-tail tandem repeats (multimers) of either HPV 16 epitope “17-36” or “69-81” or one copy (monomer) of 11-88 fused to the same residues of HPV 18 were constructed and expressed in <jats:italic>E. coli</jats:italic>. SDS-PAGE and Western blot analyses indicated the proper expression and stability of the <jats:italic>E. coli</jats:italic>-derived DT peptides. Mice immunized by formulation of the purified DT peptides and Freund’s adjuvant (CFA/IFA) raised neutralizing antibodies (NAbs; the highest for DT: 11-88 peptide) which showed proper cross-reactivity to HPV types: 18, 16, 31, and 45 and efficiently neutralized HPV 18/16 pseudoviruses <jats:italic>in vitro</jats:italic>. Immunization studies in mice by formulation of the DT: 11-88 × 1 peptide with various adjuvants (alum, MF59, and Montanides ISA 720 and 50) indicated that Montanide adjuvants elicited the highest cross-reactive titers of NAbs and similar levels of IgG1 and IgG2a (switching towards balanced Th1/Th2 responses). The results implied development of low-cost <jats:italic>E. coli</jats:italic>-derived DT: 11-88 peptide formulated in human compatible ISA 720 adjuvant as a HPV vaccine.</jats:p>

• 出版日期2018