g. TT or DT) actually inhibited the antibody response to the hapten conjugate [42]. This phenomenon, termed epitope-specific suppression or epitopic suppression [42], [43], [44] and [45], also extends to haptens conjugated to virus-like particles [46]. While both T cells and B cells have been implicated in the mechanism of epitope-specific suppression, the inhibitory effect appears to be largely due to competition with pre-existing carrier-specific Proteasome inhibitor review B cells and antibodies [47]. Importantly, epitope-specific suppression observed with gonadotropin releasing hormone (GnRH) peptide conjugated to DT could be bypassed by
conjugating GnRH to a T cell helper peptide derived from DT [48]. These results suggest that epitope suppression is restricted to memory B cell epitopes not memory T cell epitopes. Thus we expect that that nanoparticle vaccines containing TpD peptide would have the benefit
of leveraging pre-existing CD4 memory T cells without invoking B cell-mediated epitope-specific suppression. In conclusion we have developed a chimeric MHC class II memory recall peptide, TpD that gives broad MHC class II coverage in humans, and is potent in generating a recall response in mice and non-human primates. It is possible that this will be a valuable tool for providing enhanced responses against poorly immunogenic vaccines. Conflict of interest: of All authors are employees and shareholders of
Selecta Biosciences. “
“Infection with influenza A virus (IAV) causes a contagious buy Rapamycin disease that affects mainly the upper respiratory tract and is still one of the leading causes of mortality and morbidity worldwide [1] and [2]. Most vaccines against influenza A and B in use today are administered via the parenteral route. Although these vaccines can induce virus-specific systemic immune responses, they barely activate the mucosal immune system, the port of entry of the influenza viruses [3] and [4]. Nasal vaccination therefore might be a promising alternative for parenteral vaccination against influenza virus, since this route of vaccination resembles more closely natural infection and it is known to elicit both systemic and mucosal immune responses [4] and [5]. In addition, nasal vaccination might enhance vaccine efficacy in contrast to parenteral vaccination since nasal vaccination is associated with secreted IgA (SIgA) antibody production at the mucosal surfaces [5], [6] and [7]. Because SIgA forms a first line of defence against invading pathogens at the portal of entry [8], [9] and [10], it may help to prevent penetration and replication of influenza virus in the respiratory tract mucosa early after host cell invasion.