• Bivalent mucosal peptide vaccines administered using the LCP carrier system stimulate protective immune responses against Streptococcus pyogenes infection.

      Schulze, Kai; Ebensen, Thomas; Chandrudu, Saranya; Skwarczynski, Mariusz; Toth, Istvan; Olive, Colleen; Guzman, Carlos A; Helmholtz Centre for infection researchGmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-09-05)
      Despite the broad knowledge about the pathogenicity of Streptococcus pyogenes there is still a controversy about the correlate of protection in GAS infections. We aimed in further improving the immune responses stimulated against GAS comparing different vaccine formulations including bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di-AMP) and BPPCysMPEG, a derivative of the macrophage-activating lipopeptide (MALP-2), as adjuvants, respectively, to be administered with and without the universal T helper cell epitope P25 along with the optimized B cell epitope J14 of the M protein and B and T cell epitopes of SfbI. Lipopeptide based nano carrier systems (LCP) were used for efficient antigen delivery across the mucosal barrier. The stimulated immune responses were efficient in protecting mice against a respiratory challenge with a lethal dose of a heterologous S. pyogenes strain. Moreover, combination of the LCP based peptide vaccine with c-di-AMP allowed reduction of antigen dose at the same time maintaining vaccine efficacy.
    • Efficient nanoparticle-mediated needle-free transcutaneous vaccination via hair follicles requires adjuvantation.

      Mittal, Ankit; Schulze, Kai; Ebensen, Thomas; Weißmann, Sebastian; Hansen, Steffi; Lehr, Claus-Michael; Guzmán, Carlos A; Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany. (2015-01)
      Trans-follicular (TF) vaccination has recently been studied as a unique route for non-invasive transcutaneous vaccination. The present study aims to extensively characterize the immune responses triggered by TF vaccination using ovalbumin loaded chitosan-PLGA (poly lactic-co-glycolic acid) nanoparticles without skin pre-treatment to preserve skin integrity. The impact of formulation composition i.e. antigenic solution or antigen-loaded nanoparticles with or without adjuvant [bis-(3',5')-cyclic dimeric adenosine monophosphate] on immune response quality following TF immunization was analyzed and compared with immune responses obtained after tape stripping the skin. The results presented in this study confirm the ability of nanoparticle based vaccine formulations to deliver antigen across the intact skin via the follicular route, but at the same time demonstrate the necessity to include adjuvants to generate efficient antigen-specific humoral and cellular immune responses.
    • Intranasal vaccination with an adjuvanted polyphosphazenes nanoparticle-based vaccine formulation stimulates protective immune responses in mice.

      Schulze, Kai; Ebensen, Thomas; Babiuk, Lorne A; Gerdts, Volker; Guzman, Carlos A.; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany. (2017-06-01)
      The most promising strategy to sustainably prevent infectious diseases is vaccination. However, emerging as well as re-emerging diseases still constitute a considerable threat. Furthermore, lack of compliance and logistic constrains often result in the failure of vaccination campaigns. To overcome these hurdles, novel vaccination strategies need to be developed, which fulfill maximal safety requirements, show maximal efficiency and are easy to administer. Mucosal vaccines constitute promising non-invasive approaches able to match these demands. Here we demonstrate that nanoparticle (polyphosphazenes)-based vaccine formulations including c-di-AMP as adjuvant, cationic innate defense regulator peptides (IDR) and ovalbumin (OVA) as model antigen were able to stimulate strong humoral and cellular immune responses, which conferred protection against the OVA expressing influenza strain A/WSN/OVAI (H1N1). The presented results confirm the potency of nanoparticle-based vaccine formulations to deliver antigens across the mucosal barrier, but also demonstrate the necessity to include adjuvants to stimulate efficient antigen-specific immune responses.