The immunological effects of intradermal particle-based vaccine delivery using a novel microinjection needle studied in a human skin explant model.

For intradermal (ID) immunisation, novel needle-based delivery systems have been proposed as a better alternative to the Mantoux method. However, the penetration depth of needles in the human skin and its effect on immune cells residing in the different layers of the skin has not been analyzed. A novel and user-friendly silicon microinjection needle (Bella-muTM) has been developed, which allows for a perpendicular injection due to its short needle length (1.4-1.8 mm) and ultrashort bevel. We aimed to characterize the performance of this microinjection needle in the context of the delivery of a particle-based outer membrane vesicle (OMV) vaccine using an ex vivo human skin explant model. We compared the needles of 1.4 and 1.8 mm with the conventional Mantoux method to investigate the depth of vaccine injection and the capacity of the skin antigen-presenting cell (APC) to phagocytose the OMVs. The 1.4 mm needle deposited the antigen closer to the epidermis than the 1.8 mm needle or the Mantoux method. Consequently, activation of epidermal Langerhans cells was significantly higher as determined by dendrite shortening. We found that five different subsets of dermal APCs are able to phagocytose the OMV vaccine, irrespective of the device or injection method. ID delivery using the 1.4 mm needle of a OMV-based vaccine allowed epidermal and dermal APC targeting, with superior activation of Langerhans cells. This study indicates that the use of a microinjection needle improves the delivery of vaccines in the human skin.

Peptide-Based Vaccination for Antibody Responses Against HIV.

HIV-1 is responsible for a global pandemic of 35 million people and continues to spread at a rate of >2 million new infections/year. It is widely acknowledged that a protective vaccine would be the most effective means to reduce HIV-1 spread and ultimately eliminate the pandemic, whereas a therapeutic vaccine might help to mitigate the clinical course of the disease and to contribute to virus eradication strategies. However, despite more than 30 years of research, we do not have a vaccine capable of protecting against HIV-1 infection or impacting on disease progression. This, in part, denotes the challenge of identifying immunogens and vaccine modalities with a reduced risk of failure in late stage development. However, progress has been made in epitope identification for the induction of broadly neutralizing antibodies. Thus, peptide-based vaccination has become one of the challenges of this decade. While some researchers reconstitute envelope protein conformation and stabilization to conserve the epitope targeted by neutralizing antibodies, others have developed strategies based on peptide-carrier vaccines with a similar goal. Here, we will review the major peptide-carrier based approaches in the vaccine field and their application and recent development in the HIV-1 field.