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Background/Objectives: The emergence of the Omicron variant has complicated COVID-19 control and prompted vaccine updates. Recent studies have shown that a fourth dose significantly protects against infection and severe disease, though long-term immunity data remain limited. This study aimed to assess Anti-S-RBD antibodies and interferon-γ levels in healthcare workers 12 months after receiving bivalent Original/Omicron BA.4-5 fourth SARS-CoV-2 vaccine. Methods: In this prospective cohort study, 549 healthcare workers were categorized by the initial vaccination schedule, with 229 individuals having received the fourth SARS-CoV-2 vaccine dose. Blood samples were collected from all participants 12 months post-vaccination. Results: Significant differences in Anti-S-RBD antibody levels were observed between those receiving a fourth dose and those who did not, while no differences were seen in interferon-γ levels. After 12 months, there were no significant differences in humoral and cellular immunity response between volunteers primoinfected or reinfected across different periods by the Omicron variant. A multivariable analysis revealed an association between high antibody levels (>6000 U/mL) and interferon-γ levels (OR: 3.13; 95% CI: 1.3–7.7; p < 0.05). Regarding primary vaccine schedules, participants vaccinated with ChAdOx1 (a single or double dose) had notably lower antibody levels compared to those who received mRNA-based vaccines. Additionally, the study shows a higher frequency of multiple infections among those with a single-dose ChAdOx1 primary schedule (OR: 6.24; 95% CI: 1.25–31.15; p < 0.01). Conclusions: Overall, mRNA-based vaccines exhibited stronger long-term immunogenicity. Repeated exposure to the Omicron variant seems to mitigate immune imprinting from the wild-type SARS-CoV-2. An association was observed between high antibody levels and a strong cellular response, although the correlation was not linear. [ABSTRACT FROM AUTHOR]

The immune response of liver transplant (LT) recipients to a third dose of the BNT162b2 mRNA vaccine significantly waned after four months. We aimed to evaluate the immune response and breakthrough infection rates of a fourth dose against the Omicron variants among LT recipients. LT recipients who had no past or active SARS-CoV-2 infection and received three doses of the BNT162b2mRNA vaccine were included. Of the 73 LT recipients, 50 (68.5%) received a fourth dose. The fourth dose was associated with a significantly higher positive immune response than the third dose. Receptor-binding domain (RBD) IgG and Omicron BA.1 and BA.2 neutralizing antibodies were determined at a median of 132 and 29 days after the third and fourth vaccines. They were 345 binding antibody units per milliliter (BAU/mL) vs. 2118 BAU/mL (p < 0.0001), 10 vs. 87 (p < 0.0001), and 15 vs. 149 (p = 0.001), respectively. Breakthrough infections were documented among nine (18%) LT recipients after the fourth dose and among seven (30.4%) patients following the third dose (p = 0.2); 93.5% of breakthrough infections were mild. The infection rate after the fourth dose was higher among diabetic vs. nondiabetic recipients (33.3% vs. 6.9%, respectively; p = 0.02). Further studies are needed to evaluate additional factors influencing the breakthrough infection rate among LT recipients. [ABSTRACT FROM AUTHOR]

Background: In the ongoing COVID-19 pandemic, advanced age is a risk factor for a severe clinical course of SARS-CoV-2 infection. Thus, older people may benefit in particular from booster doses with potent vaccines and research should focus on optimal vaccination schedules. In addition to each individual's medical history, immunosenescence warrants further research in this population. This study investigates vaccine-induced immune response over 1 year.Methods/design: EU-COVAT-1-AGED is a randomised controlled, adaptive, multicentre phase II protocol evaluating different booster strategies in individuals aged ≥75 years (n=600) already vaccinated against SARS-CoV-2. The initial protocol foresaw a 3rd vaccination (1st booster) as study intervention. The present modified Part B of this trial foresees testing of mRNA-1273 (Spikevax®) vs. BNT162b2 (Comirnaty®) as 4th vaccination dose (2nd booster) for comparative assessment of their immunogenicity and safety against SARS-CoV-2 wild-type and variants. The primary endpoint of the trial is to assess the rate of 2-fold antibody titre increase 14 days after vaccination measured by quantitative enzyme-linked immunosorbent assay (Anti-RBD-ELISA) against wild-type virus. Secondary endpoints include the changes in neutralising antibody titres (Virus Neutralisation Assay) against wild-type as well as against Variants of Concern (VOC) at 14 days and up to 12 months. T cell response measured by qPCR will be performed in subgroups at 14 days as exploratory endpoint. Biobanking samples are being collected for neutralising antibody titres against potential future VOC. Furthermore, potential correlates between humoral immune response, T cell response and neutralising capacity will be assessed. The primary endpoint analysis will be triggered as soon as for all patients the primary endpoint (14 days after the 4th vaccination dose) has been observed.Discussion: The EU-COVAT-1-AGED trial Part B compares immunogenicity and safety of mRNA-1273 (Spikevax®) and BNT162b2 (Comirnaty®) as 4th SARS-CoV-2 vaccine dose in adults ≥75 years of age. The findings of this trial have the potential to optimise the COVID-19 vaccination strategy for this at-risk population.Trial Registration: ClinicalTrials.gov NCT05160766 . Registered on 16 December 2021.Protocol Version: V06_0: 27 July 2022. [ABSTRACT FROM AUTHOR]

Solid organ transplant recipients (SOTRs) show higher rates of COVID-19 breakthrough infection than the general population, and nowadays, vaccination is the key preventative strategy. Nonetheless, SOTRs show lower vaccine efficacy for the prevention of severe COVID-19. Moreover, the emergence of new SARS-CoV-2 variants of concern has highlighted the need to improve vaccine-induced immune responses by the administration of repeated booster doses. In this study, we analyzed the humoral and cellular responses in a cohort of 25 SOTRs, including 15 never-infected SOTRs who received the fourth dose of the mRNA vaccine and 10 SOTRs who contracted SARS-CoV-2 infection after the third dose. We analyzed the serum IgG and IgA levels through CLIA or ELISA, respectively, and the Spike-specific T cells by ELISpot assay. We report a significant increase in anti-Spike IgG and no differences in IgA secretion in both groups of patients before and after the booster dose or the natural infection. Still, we show higher IgA levels in recovered SOTRs compared to the fourth dose recipients. Conversely, we show the maintenance of a positive Spike-specific T-cell response in SOTRs who received the fourth dose, which, instead, was significantly increased in SOTRs who contracted the infection. Our results suggest that the booster, either through the fourth dose or natural infection, in vulnerable poor responder SOTRs, improves both humoral and cellular-specific immune responses against SARS-CoV-2. [ABSTRACT FROM AUTHOR]