Association between Reactogenicity and Immunogenicity in a Vaccinated Cohort with Two mRNA SARS-CoV-2 Vaccines at a High-Complexity Reference Hospital: A Post Hoc Analysis on Immunology Aspects of a Prospective Cohort Study.

Enhancing our comprehension of mRNA vaccines may facilitate the future design of novel vaccines aimed at augmenting immune protection while minimising reactogenic responses. Before this design is carried out, it is important to determine whether adaptive immunity correlates with the reactogenicity profile of vaccines. We studied a large cohort that was vaccinated with mRNA vaccines to answer this question. This was an observational study with real-world data. Reactogenicity data were obtained from the VigilVacCOVID study. Immunogenicity (humoral and cellular) data were retrieved from health records. One main population (n = 215) and two subpopulations were defined (subpopulation 1, n = 3563; subpopulation 2, n = 597). Sensitivity analyses were performed with subpopulations 1 and 2 to explore the consistency of results. We analysed the association of the intensity and types of adverse reactions with the development and quantity of elicited antibody titres. As an exploratory analysis in subpopulation 1, we assessed the association between reactogenicity and cellular immunogenicity. A higher incidence of fever, malaise, and myalgia including severe cases was significantly associated with the development and quantity of positive antibody titres. No significant findings were observed with cellular immunity. We observed a positive association between immunogenicity and reactogenicity. These findings can be relevant for the future development of our understanding of how mRNA vaccines function.

Academic challenges on advanced therapy medicinal products' development: a regulatory perspective.

Advanced therapy medicinal products (ATMPs) are becoming the new kid on the block for the treatment of a variety of indications with promising results. Despite the academic contribution to the basic and clinical research of ATMPs, undertaking a full product development process is extraordinarily challenging and demanding for academic institutions. Meeting regulatory requirements is probably the most challenging aspect of academic development, considering the limited experience and resources compared with pharmaceutical companies. This review aims to outline the key aspects to be considered when developing novel ATMPs from an academic perspective, based on the results of our own experience and interaction with the Spanish Agency of Medicines and Medical Devices (AEMPS) and European Medicine Agency (EMA) related to a number of academic ATMP initiatives carried out at our center during the last 5 years. Emphasis is placed on understanding the regulatory requirements during the early phases of the drug development process, particularly for the preparation of a Clinical Trial Application. Academic centers usually lack expertise in product-related documentation (such as the Investigational Medicinal Product Dossier), and therefore, early interaction with regulators is crucial to understand their requirements and receive guidance to comply with them. Insights are shared on managing quality, nonclinical, clinical, and risk and benefit documentation, based on our own experience and challenges. This review aims to empower academic and clinical settings by providing crucial regulatory knowledge to smooth the regulatory journey of ATMPs.

Tolerability and Reactogenicity Profile of mRNA SARS-Cov-2 Vaccines from a Mass Vaccination Campaign in a Tertiary Hospital: Between-Vaccine and Between-Population Prospective Observational Study (VigilVacCOVID Study).

BACKGROUND: The comparative safety profile of SARS-Cov2 vaccines requires further characterization in real-world settings. OBJECTIVES: The aim of the VigilVacCOVID study was to assess the short-term safety of BNT162b2 and mRNA-1273 during the vaccination campaign of healthcare professionals (HCPs) and solid-organ transplant recipients (SOTRs) at a hospital clinic. METHODS: We conducted an observational, prospective, single-center, post-authorization study to characterize short-term adverse reactions (ARs) after vaccination. The primary endpoint was to assess between-vaccine differences (HCPs receiving BNT162b2 or mRNA-1273) and between-population differences (HCPs and SOTRs, both receiving mRNA-1273) in the risk of any ARs. Propensity score and covariate-adjusted multivariate models were used. The key secondary endpoint was to provide a descriptive assessment of the frequencies and intensity distribution of ARs. RESULTS: We included 5088 HCPs and 1289 patients. mRNA-1273 showed greater reactogenicity than BNT162b2, with an odds ratio (OR) for any AR of 3.04 (95% confidence interval (CI) 2.48-3.73; p value: < 0.001) and a higher frequency and intensity of reported ARs. Compared with HCPs vaccinated with mRNA-1273, SOTRs showed a lower risk of ARs (OR = 0.36; 95% CI 0.25-0.50), with fewer and less severe ARs. Age, sex, and previous SARS-CoV-2 infection were statistically significant covariates for the risk of any AR. A history of drug allergy was significant in the comparison between vaccines (BNT162b2 vs. mRNA-1273), but not in that between SOTRs and HCPs. CONCLUSIONS: Our study shows that mRNA-1273 had greater reactogenicity than BNT162b2. Overall, both vaccines had an adequate tolerability profile. mRNA-1273 vaccination caused fewer ARs with milder severity in SOTRs.