T cell-dependent antigen adjuvanted with DOTAP-CpG-B but not DOTAP-CpG-A induces robust germinal center responses and high affinity antibodies in mice

5 years ago

T cell-dependent antigen adjuvanted with DOTAP-CpG-B but not DOTAP-CpG-A induces robust germinal center responses and high affinity antibodies in mice

Chen-Feng Qi, Pietro Miozzo, Billur Akkaya, Mirna Pena, Susan K. Pierce, Patrick W. Sheehan, Silvia Bolland, Munir Akkaya, Javier Manzella-Lapeira

The development of vaccines for infectious diseases for which we currently have none, including HIV, will likely require the use of adjuvants that strongly promote germinal center responses and somatic hypermutation to produce broadly neutralizing antibodies. Here we compared the outcome of immunization with the T-cell dependent antigen, NP-conjugated to chicken gamma globulin (NP-CGG) adjuvanted with the toll-like receptor 9 (TLR9) ligands, CpG-A or CpG-B, alone or conjugated with the cationic lipid carrier, DOTAP. We provide evidence that only NP-CGG adjuvanted with DOTAP-CpG-B was an effective vaccine in mice resulting in robust germinal center responses, isotype switching and high affinity NP-specific antibodies. The effectiveness of DOTAP-CpG-B as an adjuvant was dependent on the expression of the TLR9 signaling adaptor MyD88 in immunized mice. These results indicate DOTAP-CpG-B but not DOTAP-CpG-A is an effective adjuvant for T cell-dependent protein antigen-based vaccines. Conjugation of CpG containing synthetic ODNs with DOTAP leads to an increase in their immune-adjuvant potential in a ODN type dependent fashion. Mice immunized with a T cell dependent antigen (NP-CGG) adjuvanted with unconjugated CpG-A or CpG-B fail to generate strong immune response. On the other hand immunization of mice with NP-CGG adjuvanted with DOTAP conjugated CpG-B but not CpG-A lead to a strong antigen specific immune response.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/eji.201747113