Next-Generation Vaccines Against COVID-19 Variants: Beyond the Spike Protein.

Vaccines are among the most effective medical countermeasures against infectious diseases. The current Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spurred the scientific strategies to fight against the disease. Since 2020, a great number of vaccines based on different platforms have been in development in response to the pandemic, among which mRNA, adenoviral vector, and subunit vaccines have been clinically approved for use in humans. These first-generation COVID-19 vaccines largely target the viral spike (S) protein and aim for eliciting potent neutralizing antibodies. With the emergence of SARS-CoV-2 variants, especially the highly transmissible Omicron strains, the S-based vaccine strategies have been faced constant challenges due to strong immune escape by the variants. The coronavirus nucleocapsid (N) is one of the viral proteins that induces strong T-cell immunity and is more conserved across different SARS-CoV-2 variants. Inclusion of N in the development of COVID-19 vaccines has been reported. Here, we briefly reviewed and discussed COVID-19 disease, current S-based vaccine strategies, and focused on the immunobiology of N protein in SARS-CoV-2 host immunity, as well as the next-generation vaccine strategies involving N protein, to combat current and emerging SARS-CoV-2 variants.

疫苗是对抗传染病最有效的医学手段之一。当前由严重急性呼吸综合征冠状病毒2（SARS-CoV - 2）引发的2019冠状病毒病（COVID - 19）大流行，激发了抗击该疾病的科学策略。自2020年以来，针对此次大流行，大量基于不同平台的疫苗一直在研发中，其中信使核糖核酸（mRNA）疫苗、腺病毒载体疫苗和亚单位疫苗已获临床批准用于人类。这些第一代COVID - 19疫苗主要针对病毒刺突（S）蛋白，旨在引发强效中和抗体。随着SARS-CoV - 2变异株的出现，特别是高传染性的奥密克戎毒株，由于变异株的强免疫逃逸，基于S蛋白的疫苗策略面临持续挑战。冠状病毒核衣壳（N）是一种能诱导强烈T细胞免疫且在不同SARS-CoV - 2变异株中更为保守的病毒蛋白。已有将N蛋白用于COVID - 19疫苗研发的相关报道。在此，我们简要回顾和讨论了COVID - 19疾病、当前基于S蛋白的疫苗策略，并重点关注了SARS-CoV - 2宿主免疫中N蛋白的免疫生物学，以及涉及N蛋白的下一代疫苗策略，以对抗当前和新出现的SARS-CoV - 2变异株。