RESUMEN
Background: Due to findings on adverse reactions and clinical efficacy of different vaccinations against SARS-CoV-2, the administration of vaccination regimens containing both adenoviral vector vaccines and mRNA-based vaccines has become common. Data are still needed on the direct comparison of immunogenicity for these different regimens. Methods: We compared markers for immunogenicity (anti-S1 IgG/IgA, neutralizing antibodies, and T-cell response) with three different vaccination regimens (homologous ChAdOx1 nCoV-19 (n = 103), or mixture of ChAdOx1 nCoV-19 with mRNA-1273 (n = 116) or BNT162b2 (n = 105)) at two time points: the day of the second vaccination as a baseline and 14 days later. Results: All examined vaccination regimens elicited measurable immune responses that were significantly enhanced after the second dose. Homologous ChAdOx1 nCoV-19 was markedly inferior in immunogenicity to all other examined regimens after administration of the second dose. Between the heterologous regimens, mRNA-1273 as second dose induced greater antibody responses than BNT162b2, with no difference found for neutralizing antibodies and T-cell response. Discussion: While these findings allow no prediction about clinical protection, from an immunological point of view, vaccination against SARS-CoV-2 with an mRNA-based vaccine at one or both time points appears preferable to homologous vaccination with ChAdOx1 nCoV-19. Whether or not the demonstrated differences between the heterologous regimens are of clinical significance will be subject to further research.
RESUMEN
BACKGROUND: Paired associative stimulation (PAS) is the repeated combination of a sensory stimulus with transcranial magnetic stimulation (TMS) in close temporal association. Recently, a study demonstrated that PAS of an auditory stimulus together with TMS of the temporal cortex is capable of changing the amplitude of auditory evoked potentials (AEP). OBJECTIVE: This study examined the influence of tone duration and habituation in temporal cortex PAS as elicited by 40 and 20 Hz amplitude modulated auditory steady-state responses (aSSR). METHODS: Eighteen subjects participated in two experiments, including two PAS protocols each, which consisted of 200 auditory stimuli (4 kHz) paired with temporal cortex TMS with an interstimulus interval (ISI) of 45 ms between tone onset and TMS pulse, delivered at 0.1 Hz. Experiment 1 compared auditory stimuli with different lengths [PAS (23 ms) vs. PAS (400 ms)]. Experiment 2 investigated verum vs. sham PAS. aSSR for the paired tone (4 kHz) and a control tone (1 kHz) were measured pre- and post-interventional-using 40 Hz aSSR in experiment 1 and both 20 and 40 Hz aSSR in experiment 2. RESULTS: A statistically significant, sham-controlled decrease in amplitude was observed for the 20 Hz aSSR using the 4 kHz PAS carrier frequency in experiment 2. CONCLUSION: Frequency-specific effects for the 20 Hz aSSR confirm the feasibility of auditory PAS and highlight the secondary auditory cortex as its target site, introducing new possible treatment protocols for patients suffering from tinnitus. The amplitude decrease can be explained by principles of spike timing-dependent plasticity and the superposition model of aSSR.
