Introduction
The acute infectious disease coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is characterized by fever and upper respiratory symptoms, and even multiple organ failure such as acute respiratory distress syndrome [1]. COVID-19 began to appear in December 2019 and posed a huge threat to global public health and human life. The World Health Organization (WHO) declared that COVID-19 has become a global pandemic in March 2020. COVID-19 spread across nearly every country. Up to now, COVID-19 has accumulated more than 661 million confirmed cases and more than 6.7 million deaths worldwide.
Vaccination is the most effective way to prevent SARS-CoV-2 infection. At present, many types of vaccines against SARS-CoV-2 have been widely vaccinated in the world and achieved certain preventive effects. Among them, recombinant SARS-CoV-2 vaccine with adenovirus type 5 vector, which was developed and produced in China (Ad5-nCoV, CanSinoBIO, China), has been proved to induce high level of both humoral and cellular immune responses [2-4]. Importantly, Ad5-nCoV has been widely vaccinated in the population and approved by WHO as COVID-19 vaccine ”Emergency Use List” in May 2022 [5-7].
SARS-CoV-2 is single positive-stranded, enveloped RNA virus that can infect many animal species and humans. The genome containing six open reading frames (ORFs), which encode non-structural proteins such as RNA dependent RNA polymerase (RdRp), and four structure proteins, namely spike protein (S), envelope protein (E), membrane protein (M) and nucleocapsid proteins (N) [8]. The S protein could induce high level of specific antibody. However, antibody responses against SARS-CoV-2 always could not be well maintained for a long time [9].
It has been reported that SARS-CoV-2-specific CD8+ T cell responses in peripheral blood of COVID-19 patients were closely related to remission of the disease [10, 11]. In fact, SARS-CoV-2 specific CD8+ T cell responses could be detected in acute phase of COVID-19 within 7 days after onset of symptoms, which always reached the strongest at 14 days [12]. Studies in SARS-CoV-2 infected animal models have found that although neutralizing antibodies could protect against viral attack, CD8+ T cell responses could provide more important clinical protection when antibody levels were low or reduced [13]. CD8+ T cell epitopes of SARS-CoV-2 restricted by classical HLA-Ⅰ molecules, such as HLA-A1/ORF1a1637, HLA-A2/S269, HLA-A3/N361, HLA-A24/S1208, HLA-B7/N105 and HLA-B40/N322, were used to further study the effects and mechanisms of specific CD8+ T cell responses in SARS-CoV-2 infection [14, 15]. Among them, NP105-113 epitope restricted by HLA-B7 has been proved to induce specific CD8+ T cell response with strong antiviral activity [16]. Although most studies focused on classical HLA-Ⅰ restricted CD8+ T cell epitopes and specific responses, non-classical HLA-Ⅰ molecule HLA-E restricted CD8+ T cells also play an important role for immune protection and regulation in many viral infectious diseases [17-19]. Notably, HLA-E is a ubiquitous HLA locus with only two different alleles HLA-E*0101 and HLA-E*0103, both of which have a combined frequency of over 99% in global population. The two molecules just differ in position 107 of the mature HLA-E protein (arginine for HLA-E*0101 and glycine for HLA-E*0103)[20]. It has been proposed to use HLA-E restricted CD8+ T cells to treat severe COVID-19 patients in the early stage of SARS-CoV-2 infection [21]. Therefore, it is necessary to identify CD8+ T cell epitopes that can overcome the polymorphism of HLA molecules. Moreover, detection of SARS-CoV-2 epitope-specific CD8+ T cell responses may be important for evaluation of the protective effects induced by SARS-CoV-2 vaccines.
In this study, specific CD8+ T cell responses in different vaccines inoculated populations, especially in Ad5-nCoV vaccinated subjects, were detected based on identification of four epitopes on S protein of SARS-CoV-2 restricted by both HLA-E*0101 and E*0103. These findings may provide crucial information to evaluate the effects of COVID-19 vaccines immunization in population according to HLA-E-restricted SARS-CoV-2 specific CD8+ T cell responses.