COVID-19 vaccine development

正在对收集的人体样本进行分析，以详细检查自然感染后的体液和细胞免疫。在一项批准的临床试验中，这些患者从感染中恢复并接受捐献恢复期血浆用于转移给住院患者。对这些队列的免疫反应进行了纵向研究，以确定免疫反应的性质和寿命。此外，将对受体患者进行研究，以确定血浆移植后免疫治疗的益处。自然感染的分析结果对疫苗策略的设计具有重要意义。鉴定具有高滴度中和抗体的患者也将支持血浆收集的选择，以便作为免疫治疗转移给住院患者。我们研究了希腊雅典感染的恢复期人群中SARS-CoV-2抗体维持情况。COVID-19发病后8个月的SARS-CoV-2抗体动力学：在24%的恢复期血浆供者中观察到刺突抗体的持续存在，但中性抗体的丧失。我们继续对该队列进行14个月的随访，并确定抗体寿命和中和活性。我们与费尔伯博士的部门合作，开发了DNA载体，在两次接种后诱导猕猴产生强烈的免疫反应。我们的策略是诱导既能中和抗体又能最佳抑制病毒感染的细胞免疫。几种形式的SARS-CoV-2抗原在DNA载体中表达，并在鉴定后在动物中进行了测试。猕猴疫苗接种表明，这些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具有保护作用，从而为基于DNA技术开发针对SARS-CoV-2的预防性疫苗提供了机会，这种疫苗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更长的寿命和有效性。我们在抗原naive和之前感染过2019冠状病毒病（COVID-19）的个体（NCT04743388）中表征了细胞因子和趋化因子对第一剂和第二剂BNT162b2 mRNA（辉瑞/BioNtech）疫苗的反应。增强后早期白细胞介素-15 （IL-15）和干扰素γ (ifn - γ)水平的短暂升高与Spike抗体水平相关，支持它们作为疫苗接种后有效体液免疫发展的生物标志物。我们发现了一个系统性的特征，包括第一次接种后IL-15、ifn - γ和IP-10/CXCL10的增加，第二次接种后肿瘤坏死因子α (tnf - α)和IL-6的富集。在先前感染covid -19的个体中，单次接种疫苗可产生强烈的细胞因子诱导和抗体滴度，与抗原初始个体加强接种疫苗后观察到的抗体滴度相似，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.