ABSTRACT
Several vaccines have been found effective against COVID-19, usually administered in homologous regimens, with the same vaccine used for the prime and boost doses. However, recent studies have demonstrated improved protection via heterologous mix-and-match COVID-19 vaccine combinations, and a direct comparison among these regimens is needed to identify the best employment strategies. Here, we show a single-cohort comparison of changes to the humoral and cellular immune compartments following five different COVID-19 vaccines spanning three technologies (adenoviral, mRNA and inactivated vaccines). These vaccines were administered in a combinatorial fashion, resulting in sixteen different homologous and heterologous regimens. SARS-CoV-2-targeting antibody titres were highest when the boost dose consisted of mRNA-1273, independent of the vaccine used for priming. Priming with BBIBP-CorV induced less class-switching among spike-binding memory B cells and the highest antigen-specific T cell responses in heterologous combinations. These were generally more immunogenic in terms of specific antibodies and cellular responses compared to homologous regimens. Finally, single-cell analysis of 754 samples revealed specific B and T cell signatures of the vaccination regimens, indicating distinctive differences in the immune responses. These data provide new insights on the immunological effects of COVID-19 vaccine combinations and a framework for the design of improved vaccination strategies for other pathogens and cancer.
Subject(s)
COVID-19 , NeoplasmsABSTRACT
Passive immunotherapy has been evaluated as a therapeutic alternative for patients with COVID-19 disease. Equine polyclonal immunotherapy for COVID-19 (EPIC) showed adequate safety and potential efficacy in a clinical trial setting and obtained emergency use authorisation in Argentina. We studied its utility in a real world setting with a larger population. Methods: We conducted a retrospective cohort study at "Hospital de Campana Escuela-Hogar" in Corrientes, Argentina, to assess safety and effectiveness of EPIC in hospitalized adults with severe COVID-19 pneumonia. Primary endpoints were 28-days all cause mortality and safety. Mortality and improvement in modified WHO clinical scale at 14 and 21 days were secondary endpoints. Potential confounder adjustment was made by logistic regression weighted by the inverse of the probability of receiving the treatment (IPTW) and doubly robust approach. Results: Clinical records of 395 exposed (EPIC) and 446 non-exposed (Controls) patients admitted between November 2020 and April 2021 were analyzed. Median age was 58 years, 56.8% males. Mortality at 28 days was 15.7% ( EPIC) vs 21.5% (Control). After IPTW adjustment the OR was 0.66 (95 % CI: 0.46 - 0.96) p= 0.03. The effect was more evident in the subgroup who received two EPIC doses (complete treatment, n=379), OR 0.58 (95% CI 0.39 to 0.85) p=0.005. Overall and serious adverse events were not significantly different between groups.