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.
Subject(s)
COVID-19 , PneumoniaABSTRACT
Background: The safety, efficacy and humoral immune-response to Sputnik-V were independently evaluated. Since SARS-CoV-2 lineage P.1 is rapidly spreading in Argentina and the neutralization of P.1 by Sputnik-V-elicited sera has not been determined yet, we evaluated efficacy of Sputnik-V-immunized humoral response faced to P.1.Methods: The safety/efficacy of Sputnik-V were assessed by monitoring self-reported adverse events and disease rate among Health-Care Workers (HCW) who received both doses, within 4 months. Immunogenicity of the vaccine was evaluated by measuring anti-Spike (S) IgG antibodies (Abs) and neutralizing antibodies (NAb) prior to, 14 and 42 days after-vaccination. To determine the effectiveness of pre-existing NAb against P.1, samples were analysed from individuals: A-recovered from SARS-CoV-2 wild type B.1 (WT) infection, B-recovered from WT infection and received one/two doses of Sputnik-V, and C-without previous infection and received one/two doses of Sputnik-V.Findings: A total of 285 HCW were recruited, all reporting good tolerance, without severe adverse events. Sputnik showed 97·60% efficacy against COVID-19 during the observation period. At day 42, 99·65% of the individuals had anti-S IgG; however, 23·15% had not detectable NAb. The NAb ability against the SARS-CoV-2 strains showed significantly higher neutralization levels against WT compared to P.1 (p<0·001), with only a few samples not able to neutralize P.1.Interpretation: We corroborated that Sputnik-V is safe and induces an efficient humoral immune response, although not all immunized subjects developed NAb. While few samples failed to neutralize P.1, the variant does not escape from Sputnik-V-elicited immunity neither from immunity by WT infection.Funding Information: This work was supported by the Fondo para la Investigación Científica y Tecnológica (FONCyT) [PICT IP COVID 19-0464, 2020]; School of Medical Sciences, National University of Córdoba, Argentina and the Ministry of Health of Córdoba, Argentina.Declaration of Interests: The authors state that they have no conflicts of interest to declare.Ethics Approval Statement: This report has been performed in accordance with specific local regulations (provision number 32/2016, dated September 8, 2016, by the Council for the Ethical Evaluation of Health Research, Ministry of Health of Córdoba province, Argentina). The study observed the ethical standards established in the Declaration of Helsinki in 1964 and its subsequent modifications.