A LAG3-interfering oligonucleotide acts as an adjuvant to enhance the antibody responses induced by recombinant protein vaccines and inactivated influenza virus vaccines

• Published in: Applied microbiology and biotechnology Vol. 103; no. 16; pp. 6543 - 6557
• Main Authors: Li, Zhiqin, Song, Yilan, Cui, Cuiyun, Lan, Yu, Li, Xin, Liu, Ye, Lu, Fangjie, Zhang, Ya, Yu, Yongli, Wang, Liying
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2019; Springer; Springer Nature B.V
• Subjects: Adjuvants, Immunologic - administration & dosage; Animals; Antagonists; Antibodies; Antibodies, Viral - blood; Antibody Formation; Antigens; Antigens, CD - biosynthesis; Antisense oligonucleotides; B cells; Biomedical and Life Sciences; Biotechnological Products and Process Engineering; Biotechnology; CD223 antigen; CD4 antigen; Cell activation; Cell proliferation; Down-Regulation; Gene expression; Immune system; Immunotherapy; Influenza; Influenza vaccines; Influenza Vaccines - administration & dosage; Influenza Vaccines - immunology; Influenza viruses; Interleukin 2; Interleukin 6; Life Sciences; Lymphocytes; Lymphocytes B; Lymphocytes T; Mice; Microbial Genetics and Genomics; Microbiology; mRNA; Nucleic acids; Oligodeoxyribonucleotides, Antisense - administration & dosage; Proteins; Recombinant proteins; Recombinant Proteins - administration & dosage; Recombinant Proteins - immunology; RNA; T cells; Vaccines; Vaccines, Inactivated - administration & dosage; Vaccines, Inactivated - immunology; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - immunology; Viruses; γ-Interferon; China; Lymphocyte activation gene-3; Vaccine; Antisense oligonucleotide; T cell
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-019-09919-4

Lymphocyte activation gene-3 (LAG3) is a transmembrane protein expressed on activated T cells and delivers inhibitory signals to render the T cells unable to effectively help B cells to produce antibodies to microbes and vaccines. Presumably, antagonizing LAG3 could enhance the antibody responses to vaccines, and LAG3 antagonists could facilitate vaccines to induce vigorous antibody responses. In this study, we designed a LAG3-interfering antisense oligonucleotide, designated as LIO-1. The LIO-1 is complementary to an identical region shared in human and mouse LAG3 mRNA. We demonstrated that LIO-1 induced the degradation of LAG3 mRNA in immune cells, decreased the LAG3 expression on CD4 + T cells, maintained the prolonged proliferation and promoted the activation of antigen-specific CD4 + T cells, and increased the production of IFN-γ, IL-2, and IL-6 in the antigen re-stimulated immune cells. In addition, we found that LIO-1 enhanced the antibody responses induced by ISA35-formulated recombinant antigen vaccine or ISA35-formulated inactivated influenza virus vaccines in mice. Thus, the LIO-1, a nucleic acid LAG3 antagonist, could facilitate vaccines to induce vigorous antibody responses and has the possibility to be used as a novel adjuvant.