Cytotoxic T lymphocytes (CTLs) are key players in fighting cancer, and their induction is a major focus in the design of therapeutic vaccines. Yet, therapeutic vaccine efficacy is limited, in part due to the suboptimal vaccine processing by antigen-presenting cells (APCs). Such processing typically takes place via the MHC class II pathway for CD4 T-cell activation and MHC class I pathway for activation of CD8 CTLs. We show that a combination of skin photochemical treatment and immunization, so-called photochemical internalization (PCI) facilitated CTL activation due to the photochemical adjuvant effect induced by photosensitizer, oxygen, and light. Mice were immunized intradermally with antigen and photosensitizer, followed by controlled light exposure. PCI-treated mice showed strong activation of CD8 T cells, with improved IFN-γ production and cytotoxicity, as compared to mice immunized without parallel PCI treatment. Surprisingly, the CD8 T-cell effector functions were not impaired in MHC class II- or CD4 T-cell-deficient mice. Moreover, PCI-based vaccination caused tumor regression independent of MHC class II or CD4 T cells presence in melanoma bearing mice. Together, the data demonstrate that PCI can act as a powerful adjuvant in cancer vaccines, even in hosts with impaired T-helper functions.

Introduction: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), substantial effort has been made to gain knowledge about the immunity elicited by infection or vaccination. Methods: We studied the kinetics of antibodies and virus neutralisation induced by vaccination with BNT162b2 in a Swiss cohort of SARS-CoV-2 naïve (n = 40) and convalescent (n = 9) persons. Blood sera were analysed in a live virus neutralisation assay and specific IgG and IgA levels were measured by enzyme-linked immunoassay and analysed by descriptive statistics. Results: Virus neutralisation was detected in all individuals 2-4 weeks after the second vaccine. Both neutralisation and antibodies remained positive for >4 months. Neutralisation and antibodies showed positive correlation, but immunoglobulin G (IgG) and immunoglobulin A (IgA) seroconversion took place 2-4 weeks faster than neutralisation. Spike-protein specific IgG levels rose significantly faster and were more stable over time than virus neutralisation titres or IgA responses. For naïve but not convalescent persons, a clear boosting effect was observed. Convalescent individuals showed faster, more robust and longer-lasting immune responses after vaccination compared to noninfected persons. No threshold could be determined for spike proteinspecific IgG or IgA that would confer protection in the neutralisation assay, implicating the need for a better correlate of protection then antibody titres alone.Conclusions: This study clearly shows the complex translation of antibody data and virus neutralisation, while supporting the evidence of a single

No abstract