COVID-19 vaccine development

正在分析一批人体样本，以详细检查自然感染后的体液和细胞免疫。这些患者从感染中恢复，并接受捐赠恢复期血浆，用于在批准的临床试验中转移给住院患者。对这些队列的免疫应答进行纵向研究，以确定免疫应答的性质和寿命。此外，将对受体患者进行研究，以确定血浆转移后免疫治疗的益处。自然感染的分析结果将在疫苗策略的设计中起重要作用。鉴定具有高滴度中和抗体的患者也将支持选择血浆采集，以转移至住院患者作为免疫治疗。我们在希腊雅典的这组感染康复者中研究了SARS-CoV-2抗体的维持。COVID-19发病后8个月的SARS-CoV-2抗体动力学：观察到24%的恢复期血浆供体中存在刺突抗体，但失去了中和抗体。我们继续跟踪该队列14个月，并确定抗体寿命和中和活性。我们与Felber博士的部门合作，开发了DNA载体，在两次接种疫苗后诱导猕猴产生强烈的免疫反应。我们的策略是同时诱导中和抗体和细胞免疫，以最佳地抑制病毒感染。几种形式的SARS-CoV-2抗原在DNA载体中表达，并在表征后在动物中进行测试。猕猴疫苗接种表明，动物产生了强大的免疫反应。我们发现这些反应在病毒攻击后是保护性的，从而提供了基于DNA技术开发针对SARS-CoV-2的预防性疫苗的机会，该技术也提供了更高的细胞免疫反应。这些反应可能导致疫苗与当前一代相比具有上级的寿命和有效性。我们表征了抗原初治和既往2019冠状病毒病（COVID-19）感染个体（NCT 04743388）对第1剂和第2剂BNT 162 b2 mRNA（辉瑞/BioNtech）疫苗的细胞因子和趋化因子反应。加强免疫后早期白细胞介素-15（IL-15）和干扰素γ（IFN-γ）水平的一过性升高与刺突抗体水平相关，支持其用作疫苗接种后有效体液免疫发展的生物标志物。我们确定了一个系统性特征，包括第一次接种后IL-15、IFN-γ和IP-10/CXCL 10的增加，第二次接种后肿瘤坏死因子α（TNF-α）和IL-6使其富集。在先前感染COVID-19的个体中，单次疫苗接种导致强烈的细胞因子诱导和抗体滴度，与在抗原初治个体中加强疫苗接种后观察到的相似，这一结果对未来的公共卫生建议具有潜在意义。

A collection of human samples is being analyzed to examine in detail humoral and cellular immunity after natural infection. These patients recovered from infection and accepted to donate convalescent plasma for transfer to hospitalized patients in an approved clinical trial. The immune response of these cohort is studied longitudinally to identify the nature and longevity of immune response. In addition, the recipient patients will be studied in an effort to identify benefits of immunotherapy after plasma transfer. The results of analysis of natural infection will be important in the design of vaccine strategies. The identification of patients with high titers of neutralizing antibodies will also support the selection of plasma collection for transfer to hospitalized patients as immunotherapy. We studied SARS-CoV-2 antibody maintenance in this cohort of infected convalescent people in Athens, Greece. SARS-CoV-2 antibody kinetics eight months from COVID-19 onset: Persistence of spike antibodies but loss of neutralizing antibodies in 24% of convalescent plasma donors was observed. We continue to follow this cohort for 14 months and we determine Antibody longevity and neutralizing activity. In collaboration with Dr. Felber's Section we have developed DNA vectors that induced strong immune response in macaques after two vaccinations. Our strategy is to induce both neutralizing Ab and also cellular immunity able to optimally suppress virus infection. Several forms of SARS-CoV-2 antigens were expressed in DNA vectors and were tested in animals after characterization. Macaque vaccination showed that the animals develop robust immune responses. We showed that these responses to be protective after virus challenge, thus giving the opportunity to develop prophylactic vaccines against SARS-CoV-2 based on DNA technology that also provides much higher cellular immune responses. These responses may lead to vaccines with superior longevity and effectiveness compared with the current generation. We characterized the cytokine and chemokine responses to the 1st and 2nd dose of the BNT162b2 mRNA (Pfizer/BioNtech) vaccine in antigen-naive and in previously coronavirus disease 2019 (COVID-19)-infected individuals (NCT04743388). Transient increases in interleukin-15 (IL-15) and interferon gamma (IFN-gamma) levels early after boost correlated with Spike antibody levels, supporting their use as biomarkers of effective humoral immunity development in response to vaccination. We identified a systemic signature including increases in IL-15, IFN-gamma, and IP-10/CXCL10 after the 1st vaccination, which were enriched by tumor necrosis factor alpha (TNF-alpha) and IL-6 after the 2nd vaccination. In previously COVID-19-infected individuals, a single vaccination resulted in both strong cytokine induction and antibody titers similar to the ones observed upon booster vaccination in antigen-naive individuals, a result with potential implication for future public health recommendations.